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Parkinson Disease: HELP
Articles by Jie Li
Based on 32 articles published since 2010
(Why 32 articles?)
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Between 2010 and 2020, Jie Li wrote the following 32 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review The Role of the Gut Microbiota in the Pathogenesis of Parkinson's Disease. 2019

Yang, Dongming / Zhao, Deming / Ali Shah, Syed Zahid / Wu, Wei / Lai, Mengyu / Zhang, Xixi / Li, Jie / Guan, Zhiling / Zhao, Huafen / Li, Wen / Gao, Hongli / Zhou, Xiangmei / Yang, Lifeng. ·Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China. · Department of Pathology, Faculty of Veterinary Sciences, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. ·Front Neurol · Pubmed #31781020.

ABSTRACT: It is well-recognized that the gut microbiota (GM) is crucial for gut function, metabolism, and energy cycles. The GM also has effects on neurological outcomes via many mechanisms, such as metabolite production and the gut-brain axis. Emerging evidence has gradually indicated that GM dysbiosis plays a role in several neurological diseases, such as Parkinson's disease (PD), Alzheimer's disease, depression, and multiple sclerosis. Several studies have observed that PD patients generally suffer from gastrointestinal disorders and GM dysbiosis prior to displaying motor symptoms, but the specific link between the GM and PD is not clearly understood. In this review, we aim to summarize what is known regarding the correlation between the GM and PD pathologies, including direct, and indirect evidence.

2 Review Excessive Daytime Sleepiness in Parkinson's Disease: Clinical Implications and Management. 2018

Shen, Yun / Huang, Jun-Ying / Li, Jie / Liu, Chun-Feng. ·Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China. · Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China. ·Chin Med J (Engl) · Pubmed #29664059.

ABSTRACT: Objective: Excessive daytime sleepiness (EDS) is one of the most common sleep abnormalities in patients with Parkinson's disease (PD), yet its multifactorial etiology complicates its treatment. This review summarized recent studies on the epidemiology, etiology, clinical implications, associated features, and evaluation of EDS in PD. The efficacy of pharmacologic and non-pharmacologic treatments for EDS in PD was also reviewed. Data Sources: English language articles indexed in PubMed and Cochrane databases and Chinese-language papers indexed in Wanfang and National Knowledge Infrastructure databases that were published between January 1987 and November 2017 were located using the following search terms: "sleepiness", "sleep and Parkinson's disease", and "Parkinson's disease and treatment". Study Selection: Original research articles and critical reviews related to EDS in PD were selected. Results: EDS is a major health hazard and is associated with many motor and nonmotor symptoms of PD. Its causes are multifactorial. There are few specific guidelines for the treatment of EDS in PD. It is first necessary to identify and treat any possible factors causing EDS. Recent studies showed that some nonpharmacologic (i.e., cognitive behavioral therapy, light therapy, and repetitive transcranial magnetic stimulation) and pharmacologic (i.e., modafinil, methylphenidate, caffeine, istradefylline, sodium oxybate, and atomoxetine) treatments may be effective in treating EDS in PD. Conclusions: EDS is common in the PD population and can have an immensely negative impact on quality of life. Its causes are multifactorial, which complicates its treatment. Further investigations are required to determine the safety and efficacy of potential therapies and to develop novel treatment approaches for EDS in PD.

3 Review Protein-Restricted Diets for Ameliorating Motor Fluctuations in Parkinson's Disease. 2017

Wang, Luxi / Xiong, Nian / Huang, Jinsha / Guo, Shiyi / Liu, Ling / Han, Chao / Zhang, Guoxin / Jiang, Haiyang / Ma, Kai / Xia, Yun / Xu, Xiaoyun / Li, Jie / Liu, Jing Y / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China. · Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and TechnologyWuhan, China. ·Front Aging Neurosci · Pubmed #28701947.

ABSTRACT: Levodopa is considered to be the most effective symptomatic drug for Parkinson's disease (PD). As the disease progresses, however, the patients are likely to experience a reduced response to levodopa and develop motor fluctuations (i.e., end-of-dose wearing off and unpredictable "on-off"). Protein-rich diets and elevated plasma concentrations of large neutral amino acids have been proved to impair the therapeutic effect of levodopa by reducing its absorption and influx into the brain. On the other hand, the protein-restricted diets including low-protein diet (LPD), protein-redistribution diet (PRD) and PRD with use of low-protein products can all improve the efficacy of levodopa in patients with motor fluctuations. However, it should be noted that protein-restricted diets may also contribute to several side effects, including dyskinesia, weight loss, and malnutrition (e.g., protein and calcium insufficiency). Together, protein-restricted diets are an effective approach to improve motor fluctuations in PD patients, while long-term adherence to these diets requires monitoring for side effects.

4 Review RBD and Neurodegenerative Diseases. 2017

Jiang, Haiyang / Huang, Jinsha / Shen, Yan / Guo, Shiyi / Wang, Luxi / Han, Chao / Liu, Ling / Ma, Kai / Xia, Yun / Li, Jie / Xu, Xiaoyun / Xiong, Nian / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China. wangtaowh@hust.edu.cn. ·Mol Neurobiol · Pubmed #27032389.

ABSTRACT: Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disorder characterized by enacting one's dreams during the REM sleep, with most of the dreams being violent or aggressive, so that patients often come to see the doctor complaining hurting themselves or bed partners during sleep. Prevalence of RBD, based on population, is 0.38-2.01 %, but much higher in patients with neurodegenerative diseases, especially synucleinopathies. RBD may herald the emergence of synucleinopathies by decades, such that it may be used as an effective early marker of neurodegenerative diseases. Pharmaceutical treatment of RBD includes clonazepam, melatonin, pramipexole, and some newly reported medications. In this review, we summarized the clinical and PSG features of RBD, the pathophysiology and the therapy of it, focusing on the correlation between neurodegenerative diseases and RBD, in order to emphasize the significance of RBD as an early marker of neurodegenerative diseases.

5 Review A Compendium of Preparation and Application of Stem Cells in Parkinson's Disease: Current Status and Future Prospects. 2016

Shen, Yan / Huang, Jinsha / Liu, Ling / Xu, Xiaoyun / Han, Chao / Zhang, Guoxin / Jiang, Haiyang / Li, Jie / Lin, Zhicheng / Xiong, Nian / Wang, Tao. ·Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology Wuhan, China. · Department of Psychiatry, Harvard Medical School, Division of Alcohol and Drug Abuse, and Mailman Neuroscience Research Center, McLean Hospital Belmont, MA, USA. ·Front Aging Neurosci · Pubmed #27303288.

ABSTRACT: Parkinson's Disease (PD) is a progressively neurodegenerative disorder, implicitly characterized by a stepwise loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and explicitly marked by bradykinesia, rigidity, resting tremor and postural instability. Currently, therapeutic approaches available are mainly palliative strategies, including L-3,4-dihydroxy-phenylalanine (L-DOPA) replacement therapy, DA receptor agonist and deep brain stimulation (DBS) procedures. As the disease proceeds, however, the pharmacotherapeutic efficacy is inevitably worn off, worse still, implicated by side effects of motor response oscillations as well as L-DOPA induced dyskinesia (LID). Therefore, the frustrating status above has propeled the shift to cell replacement therapy (CRT), a promising restorative therapy intending to secure a long-lasting relief of patients' symptoms. By far, stem cell lines of multifarious origins have been established, which can be further categorized into embryonic stem cells (ESCs), neural stem cells (NSCs), induced neural stem cells (iNSCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs). In this review, we intend to present a compendium of preparation and application of multifarious stem cells, especially in relation to PD research and therapy. In addition, the current status, potential challenges and future prospects for practical CRT in PD patients will be elaborated as well.

6 Review Induced pluripotent stem cells and Parkinson's disease: modelling and treatment. 2016

Xu, Xiaoyun / Huang, Jinsha / Li, Jie / Liu, Ling / Han, Chao / Shen, Yan / Zhang, Guoxin / Jiang, Haiyang / Lin, Zhicheng / Xiong, Nian / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. · Department of Psychiatry, Harvard Medical School, Division of Alcohol and Drug Abuse, Mailman Neuroscience Research Center, McLean Hospital, Belmont, MA, USA. ·Cell Prolif · Pubmed #26748765.

ABSTRACT: Many neurodegenerative disorders, such as Parkinson's disease (PD), are characterized by progressive neuronal loss in different regions of the central nervous system, contributing to brain dysfunction in the relevant patients. Stem cell therapy holds great promise for PD patients, including with foetal ventral mesencephalic cells, human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Moreover, stem cells can be used to model neurodegenerative diseases in order to screen potential medication and explore their mechanisms of disease. However, related ethical issues, immunological rejection and lack of canonical grafting protocols limit common clinical use of stem cells. iPSCs, derived from reprogrammed somatic cells, provide new hope for cell replacement therapy. In this review, recent development in stem cell treatment for PD, using hiPSCs, as well as the potential value of hiPSCs in modelling for PD, have been summarized for application of iPSCs technology to clinical translation for PD treatment.

7 Clinical Trial The efficacy and safety of ropinirole prolonged release tablets as adjunctive therapy in Chinese subjects with advanced Parkinson's disease: a multicenter, double-blind, randomized, placebo-controlled study. 2013

Zhang, Zhenxin / Wang, Jian / Zhang, Xiaoying / Chen, Shengdi / Wang, Zhenfu / Zhang, Baorong / Liu, Chunfeng / Qu, Qiumin / Cheng, Yan / Li, Jie / Cao, Haijun / Cai, Meng / Zhu, Rongxuan. ·Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing, Beijing 100730, China. Electronic address: wuzhangzhenxin@medmail.com.cn. ·Parkinsonism Relat Disord · Pubmed #23932066.

ABSTRACT: AIM: The first evaluation of the efficacy and safety of ropinirole prolonged release (PR) as an adjunct to L-dopa in Chinese patients with advanced Parkinson's disease (PD) not optimally controlled with L-dopa. METHODS: In a 24-week, double-blind, placebo-controlled, parallel-group study, subjects with advanced PD were randomized 1:1 to ropinirole PR (N = 175) or placebo (N = 170) as add-on therapy to L-dopa. Primary outcome measure was change from baseline in awake time spent "off". Starting dose of ropinirole PR was 2 mg/day, titrated based on clinical response (maximum 24 mg/day). RESULTS: At week 24, the mean dose of ropinirole PR was 11.4 mg/day with a mean reduction of L-dopa from 506.6 to 411.6 mg/day. Subjects receiving ropinirole PR experienced a significant reduction of "off" time (2.1 h) compared with placebo (0.4 h). Secondary outcome measures including hours of "on" time without troublesome dyskinesis were significantly increased in the ropinirole PR group (1.7 h) compared with placebo (0.3 h). Subjects classified as responders were significantly more frequent in the ropinirole PR (22.8%) than placebo group (2.5%). Efficacy outcomes including Unified Parkinson's disease Rating Scale and PDQ-39 subscales of mobility were significantly improved in the ropinirole PR versus placebo group. The most frequent adverse event experienced in the ropinirole PR group was dyskinesia. CONCLUSIONS: This study demonstrated for the first time in Chinese subjects that ropinirole PR improved Parkinson's disease symptoms, permitting a reduction in L-dopa dose. The adverse events observed were consistent with the established safety profile of ropinirole, with no new safety signal identified.

8 Article The rs3129882/rs4248166 in 2020

Li, Jie / Jian, Lubao / Huang, Jinsha / Xiong, Nian / Wang, Tao. ·Department of Neurology, TaikangTongji (Wuhan) Hospital, Wuhan, Hubei, China. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. ·Int J Neurosci · Pubmed #32253955.

ABSTRACT:

9 Article Gold-nanourchin seeded single-walled carbon nanotube on voltammetry sensor for diagnosing neurogenerative Parkinson's disease. 2020

Zhang, Rui / Wang, Shan / Huang, Xiaoming / Yang, Yihang / Fan, Haitao / Yang, Fan / Li, Jie / Dong, Xushuai / Feng, Shaobin / Anbu, Periasamy / Gopinath, Subash C B / Xin, Tao. ·Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, No.324, Jingwu Road, Huaiyin District, Jinan, Shandong, 250021, PR China. · Department of Obstetrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, PR China. · Department of Biological Engineering, College of Engineering, Inha University, Incheon, 402-751, Republic of Korea. · Institute of Nano Electronic Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis, Malaysia; School of Bioprocess Engineering, Universiti Malaysia Perlis, 02600, Arau, Perlis, Malaysia. Electronic address: subash@unimap.edu.my. · Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250001, Shandong, China; Department of Neurosurgery, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, No.92, Aiguo Road, Nanchang, Jiangxi, 330006, China. Electronic address: drxintao@yeah.net. ·Anal Chim Acta · Pubmed #31761041.

ABSTRACT: α-synuclein is a predominantly expressing neuronal protein for understanding the neurodegenerative disorders. A diagnosing system with aggregated α-synuclein encoded by SNCA gene is necessary to make the precautionary treatment against Parkinson's disease (PD). Herein, gold-nanourchin conjugated anti-α-synuclein antibody was desired as the probe and seeded on single-walled carbon nanotube (SWCN) integrated interdigitated electrode (IDE). The surface morphology of SWCN-modified IDE and gold urchin-antibody conjugates were observed under FESEM, FETEM and AFM, the existing elements were confirmed. Voltammetry analysis revealed that the limit of fibril-formed α-synuclein detection was improved by 1000 folds (1 fM) with gold-nanourchin-antibody modified surface, compared to the surface with only antibody (1 pM). Validating the interaction of α-synuclein by Enzyme-linked Immunosorbent Assay was displayed the detection limit as 10 pM. IDE has a good reproducibility and a higher selectivity on α-synuclein as evidenced by the interactive analysis with the control proteins, PARK1 and DJ-1.

10 Article Alpha-synuclein oligomerization and dopaminergic degeneration occur synchronously in the brain and colon of MPTP-intoxicated parkinsonian monkeys. 2020

Li, Xuran / Yang, Weiwei / Li, Xin / Chen, Min / Liu, Chengwei / Li, Jie / Yu, Shun. ·Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Disorders, Beijing, China. · Laboratory of Neuroscience, Affiliated Hospital of Guilin Medical University, Guilin, China. · Department of Neurology, Beijing Daxing District Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, China. · Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Disorders, Beijing, China. Electronic address: yushun103@163.com. ·Neurosci Lett · Pubmed #31759083.

ABSTRACT: Dopaminergic (DAergic) degeneration and abnormal α-synuclein (α-syn) expression, phosphorylation and aggregation are observed in both the nigrostriatal system (NSS) and enteric nervous system (ENS) of patients with Parkinson's disease (PD). Whether these alterations in α-syn and DAergic neurons occur synchronously in the two nervous systems or follow a process that spreads from the gut to the brain remains a subject of debate. Here, in MPTP-intoxicated cynomolgus monkeys, we showed a parallel DAergic degeneration in the colon as well as in the substantia nigra and striatum (SN/STR), as indicated by reduced expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). In addition, we observed a simultaneous increase in the concentrations of total, phosphorylated, and oligomeric α-syn in the colon and SN/STR. Moreover, we identified that the above changes in α-syn were associated with an increase in the expression of polo-like kinase 2 (PLK2), an enzyme that promotes α-syn phosphorylation, and a decrease in the activity of protein phosphatase 2A (PP2A), an enzyme that facilitates α-syn dephosphorylation. Because the colonic ENS can be readily analyzed using routine biopsies, the shared pathological features between the colonic ENS and the brain NSS found in this study provide useful information for assessing and understanding the neuropathology in PD patients using colonic biopsies.

11 Article Mitochondrial DNA heteroplasmy rises in substantial nigra of aged PINK1 KO mice. 2020

Li, Jie / Xue, Chunyan / Gao, Qingtao / Tan, Jieqiong / Wan, Zhengqing. ·Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China. · Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China. Electronic address: wanzhengqing@sklmg.edu.cn. ·Biochem Biophys Res Commun · Pubmed #31727366.

ABSTRACT: Mutations in PINK1 and Parkin result in early-onset autosomal recessive Parkinson's disease (PD). PINK1/Parkin pathway maintain mitochondrial function by mediating the clearance of damaged mitochondria. However, the role of PINK1/Parkin in maintaining the balance of mtDNA heteroplasmy is still unknown. Here, we isolated mitochondrial DNA (mtDNA) from cortex, striatum and substantia nigra of wildtype (WT), PINK1 knockout (PINK1 KO) and Parkin knockout (Parkin KO) mice to analyze mtDNA heteroplasmy induced by PINK1/Parkin deficiency or aging. Our results showed that the Single Nucleotide Variants (SNVs) of late-onset somatic variants mainly increased with aging. Conversely, the early-onset somatic variants exhibited significant increase in the cortex and substantia nigra of PINK1 KO mice than WT mice of the same age. Increased average variant allele frequency was observed in aged PINK1 KO mice and in substantial nigra of aged Parkin KO mice than in WT mice. Cumulative variant allele frequency in the substantia nigra of PINK1 KO mice was significantly higher than that in WT mice, further supporting the pivotal role of PINK1 in mtDNA maintenance. This study presented a new evidence for PINK1 and Parkin in participating in mitochondrial quality control and provided clues for further revealing the role of PINK1 and Parkin in the pathogenesis of PD.

12 Article Exosomes from patients with Parkinson's disease are pathological in mice. 2019

Han, Chao / Xiong, Nian / Guo, Xingfang / Huang, Jinsha / Ma, Kai / Liu, Ling / Xia, Yun / Shen, Yan / Li, Jie / Jiang, Haiyang / Wang, Luxi / Guo, Shiyi / Xu, Xiaoyun / Zhang, Guoxin / Liu, Jingyu / Cao, Xuebing / Zhang, Zhentao / Lin, Zhicheng / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China. · Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China. · Department of Neurology, People's Hospital of Dongxihu District, Wuhan, 430040, Hubei, China. · Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Centre for Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China. · Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China. · Department of Psychiatry, Harvard Medical School; Division of Basic Neuroscience, and Mailman Neuroscience Research Center, McLean Hospital, Belmont, MA, 02478, USA. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China. wangtaowh@hust.edu.cn. ·J Mol Med (Berl) · Pubmed #31302715.

ABSTRACT: Cell-to-cell transport of risk molecules is a highly anticipated pathogenic mechanism in the initiation and progression of various neurodegenerative diseases. Extracellular exosome-mediated neuron to neuron transport of α-synuclein (α-syn) is increasingly recognized as a potential etiologic mechanism in Parkinson's disease (PD). Exosomal inflammation has also been increasingly implicated in PD pathogenesis and could trigger, facilitate, or aggravate disease development. However, these mechanisms have not been verified systematically, especially in vivo. Since serum contains abundant exosomes, the correlation between serum exosomes and PD pathogenesis remains unknown. Here, we show that exosomes from PD patient serum contain more α-syn and inflammatory factors such as IL-1β and TNF-α than neurological normal controls, eventually cause α-syn, ubiquitin, and P62 aggregation in recipient cells. More importantly, the intravenous or intrastriatal treatment of mice with exosomes from PD patient serum could evoke protein aggregation, trigger dopamine neuron degeneration, induce microglial activation, and cause apomorphine-coaxed rotation and movement defects. All these findings imply the exosome pathway as a new pathogenesis mechanism for PD, and therefore may present new targets for therapeutics. KEY MESSAGES: We have presented the evidence for a relationship between PD (Parkinson's disease) patients' serum exosomes and pathogenesis. PD patients' serum-derived exosomes could induce α-syn, ubiquitin and P62 aggregation in recipient cells. Intravenous or intrastriatal treatments of mice with PD exosomes were able to recapitulate the molecular, cellular and behavioral phenotypes of PD.

13 Article Glutamine protects against oxidative stress injury through inhibiting the activation of PI3K/Akt signaling pathway in parkinsonian cell model. 2019

Zhao, Yingqian / Wang, Qiang / Wang, Yuan / Li, Jie / Lu, Gang / Liu, Zhibin. ·Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, China. · College of Acupuncture and Moxibustion, Shaanxi University of Chinese Medicine, Qindu District, Xianyang, China. · Innovation Research Center of Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Qindu District, Xianyang, Shaanxi, China. · Shaanxi Key Laboratory of Acupuncture and Medicine, Qindu District, Xianyang, Shaanxi, China. · Innovation Research Center of Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Qindu District, Xianyang, Shaanxi, China. lzbbiology@163.com. · Shaanxi Key Laboratory of Acupuncture and Medicine, Qindu District, Xianyang, Shaanxi, China. lzbbiology@163.com. ·Environ Health Prev Med · Pubmed #30611190.

ABSTRACT: BACKGROUND: Parkinson's disease is a neurodegenerative disorder, and recent studies suggested that oxidative stress contributes to the degeneration of dopamine cell in Parkinson's disease. Glutamine also has a positive role in reducing oxidative stress damage. In this study, we hypothesized that glutamine offers protection against oxidative stress injury in 1-methyl-4-phenylpyridinium (MPP METHODS: MPP RESULTS: We showed that glutamine suppressed cytotoxicity induced by MPP CONCLUSION: These results suggest that glutamine strengthens the antioxidant capacity in PC12 cells induced by MPP

14 Article [Effects of 2018

Wang, Qiang / Liu, Zhibin / Wang, Yuan / Li, Jie / Lu, Gang / Jing, Zhenqi / Liu, Yao / Guo, Yang. ·Innovation Research Institute of Combined Acupuncture and Medicine, Shaanxi University of CM, Xianyang 712046, China; Shaanxi Key Laboratory of Combined Acupuncture and Medicine, Xianyang 712046. · Innovation Research Institute of Combined Acupuncture and Medicine, Shaanxi University of CM, Xianyang 712046, China. ·Zhongguo Zhen Jiu · Pubmed #30672240.

ABSTRACT: OBJECTIVE: To observe the effects of METHODS: Forty C57BL/6 male mice were randomly divided into a blank group, a model group, an electroacupuncture (EA) group and a medication group, 10 mice in each one. The mice in the model group, EA group and medication group were treated with 30-day nasal perfusion of LPS to establish PD model. From the first day of model establishment, the mice in the EA group were treated with electroacupuncture at bilateral "Yingxiang" (LI 20) and "Yintang" (GV 29) for 20 min, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. The mice in the medication group were treated with intraperitoneal injection of L-DOPA, 10 mg/mL, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. After treatment, the behavioristics changes were observed by using footprint analysis and swimming test score; the ultrastructure of olfactory bulb was observed by using transmission electron microscopy; the expression of GFAP in substantia nigra was measured by using western blot method. RESULTS: ① After model establishment, the mice in the model group, the EA group and medication group showed significant symptoms of quiver and fear of chill, and the BMI was significantly lower than that in the blank group (all CONCLUSION: The early treatment of

15 Article Analysis of nocturnal hypokinesia and sleep quality in Parkinson's disease. 2018

Xue, Fei / Wang, Fu-Yu / Mao, Cheng-Jie / Guo, Si-Ping / Chen, Jing / Li, Jie / Wang, Qiao-Jun / Bei, Hong-Zhe / Yu, Qian / Liu, Chun-Feng. ·Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Emergency Department, Jiangyin Hospital of Traditional Chinese Medicine, Wuxi 214400, China. · Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China. · Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China. · Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Institute of Neuroscience, Soochow University, Suzhou 215123, China. Electronic address: liuchunfeng@suda.edu.cn. ·J Clin Neurosci · Pubmed #29908717.

ABSTRACT: Nocturnal hypokinesia/akinesia and sleep disorder are believed to be common in Parkinson's disease (PD), but are often underestimated. To date, only a few studies have focused on nocturnal symptoms related to motor function and sleep quality in PD patients, and the assessments were based mainly on the subjective descriptions of the patients. In this study, we assessed the relationships between motor symptoms and sleep quality in 29 PD patients (17 PD patients reporting impaired bed mobility (IBM) and 12 patients without IBM). All the participants were monitored using multisite inertial sensors and polysomnography in sleep-monitoring rooms for whole night. Compared with PD-IBM patients, PD+IBM patients tended to have fewer turning-over episodes and smaller degree turns. Meanwhile, PD+IBM patients had worse Pittsburgh Sleep Quality Index (PSQI) and Parkinson's Disease Sleep Scale (PDSS) scores, and less total sleep time (TST) than PD-IBM patients. Spearman correlation analyses found that the number of turning-over events showed negative correlations with disease duration (r = -0.378, P < 0.05) and Unified Parkinson's Disease Rating Scale (UPDRS) axial scores (r = -0.370, P < 0.05). Moreover, TST (r = 0.505, p < 0.05) and sleep efficiency (SE) (r = 0.473, p < 0.05) positively correlated with the number of turns in bed. Multivariate linear regression analyses showed that UPDRS axial scores and the number of turns were significantly associated with TST (both p < 0.05). In conclusion, the number of turns in bed and UPDRS axial scores were two significant factors affecting sleep quality. Multisite inertial sensors can be used to quantitatively evaluate nocturnal motor functions in PD patients.

16 Article Effect of Rapid Eye Movement Sleep Behavior Disorder on Obstructive Sleep Apnea Severity and Cognition of Parkinson's Disease Patients. 2018

Huang, Jun-Ying / Zhang, Jin-Ru / Shen, Yun / Zhang, Hui-Jun / Cao, Yu-Lan / Mao, Cheng-Jie / Yang, Ya-Ping / Chen, Jing / Liu, Chun-Feng / Li, Jie. ·Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China. · Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China. · Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China. ·Chin Med J (Engl) · Pubmed #29664048.

ABSTRACT: Background: Rapid eye movement (REM) sleep behavior disorder (RBD) and obstructive sleep apnea (OSA) are the most common sleep disorders in Parkinson's disease (PD). The aim of this study was to identify whether RBD could alleviate OSA severity in PD patients and its effect on cognitive impairment. Methods: From February 2014 to May 2017, we recruited 174 PD patients from the Second Affiliated Hospital of Soochow University, all of whom underwent polysomnography (PSG). We collected clinical data, PSG results, and compared information between patients with and without RBD or OSA by analysis of covariance. We also investigated the effect of these sleep disorders on cognitive impairment using linear regression. Results: We grouped participants as follows: PD only (n = 53), PD + OSA (n = 29), PD + RBD (n = 61), and PD + RBD + OSA (n = 31). Minimum oxygen saturation (SaO Conclusions: We found that RBD alleviated OSA severity; however, RBD and OSA together exacerbated PD cognitive impairment. Further studies are needed to evaluate whether OSA treatment can improve cognition in PD.

17 Article Synaptotagmin-11 is a critical mediator of parkin-linked neurotoxicity and Parkinson's disease-like pathology. 2018

Wang, Changhe / Kang, Xinjiang / Zhou, Li / Chai, Zuying / Wu, Qihui / Huang, Rong / Xu, Huadong / Hu, Meiqin / Sun, Xiaoxuan / Sun, Suhua / Li, Jie / Jiao, Ruiying / Zuo, Panli / Zheng, Lianghong / Yue, Zhenyu / Zhou, Zhuan. ·State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China. · Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China. · College of Life Sciences, Liaocheng University, Liaocheng, 252059, China. · Key Lab of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China. · Departments of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. · State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China. zzhou@pku.edu.cn. ·Nat Commun · Pubmed #29311685.

ABSTRACT: Loss-of-function mutations in Parkin are the most common causes of autosomal recessive Parkinson's disease (PD). Many putative substrates of parkin have been reported; their pathogenic roles, however, remain obscure due to poor characterization, particularly in vivo. Here, we show that synaptotagmin-11, encoded by a PD-risk gene SYT11, is a physiological substrate of parkin and plays critical roles in mediating parkin-linked neurotoxicity. Unilateral overexpression of full-length, but not C2B-truncated, synaptotagmin-11 in the substantia nigra pars compacta (SNpc) impairs ipsilateral striatal dopamine release, causes late-onset degeneration of dopaminergic neurons, and induces progressive contralateral motor abnormalities. Mechanistically, synaptotagmin-11 impairs vesicle pool replenishment and thus dopamine release by inhibiting endocytosis. Furthermore, parkin deficiency induces synaptotagmin-11 accumulation and PD-like neurotoxicity in mouse models, which is reversed by SYT11 knockdown in the SNpc or knockout of SYT11 restricted to dopaminergic neurons. Thus, PD-like neurotoxicity induced by parkin dysfunction requires synaptotagmin-11 accumulation in SNpc dopaminergic neurons.

18 Article Pain Correlates with Sleep Disturbances in Parkinson's Disease Patients. 2018

Fu, Yun-Ting / Mao, Cheng-Jie / Ma, Li-Jing / Zhang, Hui-Jun / Wang, Yi / Li, Jie / Huang, Jun-Ying / Liu, Jun-Yi / Liu, Chun-Feng. ·Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China. · Sleep Center, The Second Affiliated Hospital of Soochow University, Suzhou, China. · Institute of Neuroscience, Soochow University, Suzhou, China. ·Pain Pract · Pubmed #28371220.

ABSTRACT: OBJECTIVES: Both sleep disorders and pain decrease quality of life in patients with Parkinson's disease (PD). However, little is known about the relationship between objective sleep disturbances and pain in patients with PD. This study aimed to (1) examine the clinical characteristics of pain in PD patients and (2) explore the correlation between pain and sleep disturbances in PD patients. METHODS: Parkinson's disease patients (N = 144) underwent extensive clinical evaluations of motor and nonmotor symptoms and characteristics of pain. Overnight video-polysomnography was also conducted. Clinical characteristics and sleep parameters were compared between PD patients with or without pain. RESULTS: Pain was reported by 75 patients (52.1%), with 49 (65.3%) reporting pain of at least moderate severity. PD patients with pain were older and had longer disease duration, more severe PD symptoms as assessed by Hoehn and Yahr stage and the Unified Parkinson's Disease Rating Scale, and higher L-dopa equivalent daily dose compared with PD patients without pain. PD patients with pain also showed significantly decreased sleep efficiency (57.06% ± 15.84% vs. 73.80% ± 12.00%, P < 0.001), increased nonrapid eye movement stage 1 (N1) sleep (33.38% ± 19.32% vs. 17.84% ± 8.48%, P < 0.001), and decreased rapid eye movement sleep (12.76% ± 8.24% vs. 16.06% ± 6.53%, P = 0.009). Binary logistic regression analysis revealed that poorer activities of daily living, depressed mood, higher percentage of N1 sleep, and lower sleep efficiency were independent predictors of pain in patients with PD. CONCLUSIONS: Musculoskeletal pain is the most common type of pain in patients with PD. Disrupted sleep continuity, altered sleep architecture, depressed mood, and compromised activities of daily living may be associated with pain in patients with PD.

19 Article Two polysomnographic features of REM sleep behavior disorder: Clinical variations insight for Parkinson's disease. 2017

Shen, Yun / Dai, Yong-Ping / Wang, Yi / Li, Jie / Xiong, Kang-Ping / Mao, Cheng-Jie / Huang, Jun-Ying / Luo, Wei-Feng / Liu, Chun-Feng. ·Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China. · Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Institute of Neuroscience, Soochow University, Suzhou 215123, China. Electronic address: liuchunfeng@suda.edu.cn. ·Parkinsonism Relat Disord · Pubmed #28923293.

ABSTRACT: INTRODUCTION: Loss of REM sleep muscle atonia (RWA) and dream-enactment behavior (DEB) are two associated features of REM sleep behavior disorder (RBD), which is frequently associated with Parkinson's disease (PD). Few studies have examined both DEB and RWA simultaneously in patients with PD. This study aimed to evaluate relationships between RWA, DEB and clinical characteristics of PD. METHODS: We conducted overnight polysomnography in 145 patients with PD. DEB (motor behaviors and/or vocalizations during REM) and increased RWA (IRWA; tonic and phasic chin EMG density ≥ 30% and ≥15%, respectively) were identified. Patients were categorized as clinical RBD (DEB and IRWA), sub-DEB positive (DEB only), subclinical RBD (IRWA only), or normal REM sleep. RESULTS: Patients with DEB had higher Hoehn and Yahr (H&Y) stage, Unified Parkinson's Disease Rating Scale (UPDRS) III score, levodopa equivalent dose(LEDs), and worse cognition. RWA was associated with H&Y stage, LEDs, cognition, and sleep structure in all patients. PD duration was associated with RWA, but not DEB. The PD patients who exhibited clinical or subclinical RBD, compared to sub-DEB positive, had higher H&Y stage, UPDRS III score and LEDs, lower cognitive score, worse sleep structure than the PD + cREM group. CONCLUSION: Both DEB and RWA were associated with severity of PD illness. Subclinical RBD might have different disease progression from sub-DEB positive. DEB symptoms may fluctuate or disappear whereas RWA may continue to develop as PD progresses. Differences in the course of DEB and RWA may reflect the difference in the degeneration process of neurodegenerative disorders.

20 Article Tonic Electromyogram Density in Multiple System Atrophy with Predominant Parkinsonism and Parkinson's Disease. 2017

Wang, Yi / Shen, Yun / Xiong, Kang-Ping / He, Pei-Cheng / Mao, Cheng-Jie / Li, Jie / Wang, Fu-Yu / Wang, Ya-Li / Huang, Jun-Ying / Liu, Chun-Feng. ·Department of Neurology and Sleep Center, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004; Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China. · Department of Neurology and Sleep Center, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004; Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004; Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China. ·Chin Med J (Engl) · Pubmed #28303851.

ABSTRACT: BACKGROUND: Both Parkinson's disease (PD) and multiple system atrophy (MSA) have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism (MSA-P) resembles PD in the manifestation of prominent parkinsonism. Whether the amount of rapid eye movement (REM) sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD. METHODS: This study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder (RBD) prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram (EMG) activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis. RESULTS: No significant difference between MSA-P group and PD group had been found in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index (AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024) and higher tonic chin EMG density (34.02 [18.48, 57.18]% vs. 8.40 [3.11, 13.06]%, P < 0.001) as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA + RBD subgroup was higher than that in PD + RBD subgroup (55.04 [26.81, 69.62]% vs. 11.40 [8.51, 20.41]%, P < 0.001). Furthermore, no evidence of any difference in tonic EMG density emerged between PD + RBD and MSA - RBD subgroups (P > 0.05). Both disease duration (P = 0.056) and AHI (P = 0.051) showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD + RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of MSA-P (β = 0.552, P < 0.001) and RBD (β = 0.433, P < 0.001) as predictors of higher tonic EMG density. CONCLUSION: Tonic chin EMG density could be a potential marker for differentiating MSA-P from PD.

21 Article HMGB1 Mediates Autophagy Dysfunction via Perturbing Beclin1-Vps34 Complex in Dopaminergic Cell Model. 2017

Huang, Jinsha / Yang, Jiaolong / Shen, Yan / Jiang, Haiyang / Han, Chao / Zhang, Guoxin / Liu, Ling / Xu, Xiaoyun / Li, Jie / Lin, Zhicheng / Xiong, Nian / Zhang, Zhentao / Xiong, Jing / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China. · Department of Neurology, Renmin Hospital, Hubei University of Medicine Shiyan, China. · Department of Psychiatry, Division of Alcohol and Drug Abuse, and Mailman Neuroscience Research Center, McLean Hospital, Harvard Medical School Belmont, MA, USA. · Department of Neurology, Renmin Hospital of Wuhan University Wuhan, China. ·Front Mol Neurosci · Pubmed #28197072.

ABSTRACT: Parkinson's disease (PD), a progressive neurodegenerative disorder, is characterized by irreversible dopaminergic neuron loss and intra-neuronal α-synuclein aggregation. High mobility group box 1 (HMGB1) has been proven to be involved in autophagy dysfunction induced by α-synuclein accumulation, and the Beclin1-vacuolar protein sorting 34 (Vps34) complex is of great importance to the initiation of autophagy. Nevertheless, the concrete interaction mechanism between HMGB1, α-synuclein and autophagy remains elusive, especially in the context of PD. Here in this study, we investigated the interaction between HMGB1 and α-synuclein in rotenone-induced PD cell models and their roles in autophagy flux. Results revealed elevated expression and cytosolic translocation of endogenous HMGB1 upon rotenone exposure. Besides, HMGB1 was found to be able to co-localize and interact with α-synuclein. Moreover, it had also been proven that HMGB1 could aggravate α-synuclein aggregation induced autophagy dysfunction via perturbing Beclin1-Vps34 complex formation. Based on these findings, we propose that HMGB1 is involved in rotenone-induced dopaminergic cell death via interacting with α-synuclein, perturbing the autophagy process, aggravating protein aggregation and finally propelling dopaminergic neurons to move from morbidity to mortality.

22 Article Genetic Variants of Microtubule Actin Cross-linking Factor 1 (MACF1) Confer Risk for Parkinson's Disease. 2017

Wang, Xin / Li, Nuomin / Xiong, Nian / You, Qi / Li, Jie / Yu, Jinlong / Qing, Hong / Wang, Tao / Cordell, Heather J / Isacson, Ole / Vance, Jeffery M / Martin, Eden R / Zhao, Ying / Cohen, Bruce M / Buttner, Edgar A / Lin, Zhicheng. ·School of Public Health, Xinxiang Medical University, 453003, Xinxiang, China. xwang120@gmail.com. · Department of Psychiatry, Harvard Medical School, Boston, MA, 02114, USA. xwang120@gmail.com. · Mailman Research Center, McLean Hospital, 115 Mill Street, Belmont, MA, 02478, USA. xwang120@gmail.com. · Department of Psychiatry, Harvard Medical School, Boston, MA, 02114, USA. · Laboratory of Psychiatric Neurogenomics, McLean Hospital, 115 Mill Street, Belmont, MA, 02478, USA. · School of Life Science, Beijing Institute of Technology, 100081, Beijing, China. · Mailman Research Center, McLean Hospital, 115 Mill Street, Belmont, MA, 02478, USA. · Harvard NeuroDiscovery Center, Harvard Medical School, Boston, MA, 02114, USA. · Department of Neurology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China. · Department of Neurology, Hubei Zhongshan Hospital, Wuhan, 430074, Hubei, China. · Tianjin Mental Health Center, Tianjin, 300222, China. · Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. · Neuroregeneration Laboratories, McLean Hospital, 115 Mill Street, Belmont, MA, 02478, USA. · Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA. · School of Pharmacy, Xinxiang Medical University, 453003, Xinxiang, China. · Department of Psychiatry, Harvard Medical School, Boston, MA, 02114, USA. zhicheng_lin@hms.harvard.edu. · Mailman Research Center, McLean Hospital, 115 Mill Street, Belmont, MA, 02478, USA. zhicheng_lin@hms.harvard.edu. · Laboratory of Psychiatric Neurogenomics, McLean Hospital, 115 Mill Street, Belmont, MA, 02478, USA. zhicheng_lin@hms.harvard.edu. · Harvard NeuroDiscovery Center, Harvard Medical School, Boston, MA, 02114, USA. zhicheng_lin@hms.harvard.edu. ·Mol Neurobiol · Pubmed #27021023.

ABSTRACT: The cytoskeleton not only provides structure, it is an active component of cell function, and in several neurodegenerative disorders, there is evidence of cytoskeletal collapse. Cytoskeletal proteins have been specifically implicated in the pathogenesis of Parkinson's disease (PD), where degeneration of dopaminergic (DA) neurons is the hallmark, but in which many factors may determine the resilience of DA neurons during aging and stress. Here we report that the human Microtubule Actin Cross-linking Factor 1 gene (MACF1), a downstream target of PD biochemical pathways, was significantly associated with PD in 713 nuclear families. A significant allelic association between PD and rs12118033, with P = 0.0098, was observed, and a P < 0.03 was observed in the association analysis by both a trend test and an allelic test. We further observed that it is the MACF1b isoform, not the MACF1a isoform, which is expressed in DA neurons from six human postmortem brains. In a Caenorhabditis elegans system, used to explore the effect of altered MACF1b on neurons, knockdown or knockout of the MACF1b orthologue vab-10 resulted in the selective loss of DA neurons, which validated MACF1's risk candidacy in PD. These findings strongly suggest that MACF1b may contribute to the genetic etiology and mechanistic causation of PD.

23 Article hVMAT2: A Target of Individualized Medication for Parkinson's Disease. 2016

Xiong, Nian / Li, Nuomin / Martin, Eden / Yu, Jinlong / Li, Jie / Liu, Jing / Lee, David Yue-Wei / Isacson, Ole / Vance, Jeffery / Qing, Hong / Wang, Tao / Lin, Zhicheng. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China. · School of Life Sciences, Beijing Institute of Technology, 100081, Beijing, China. · Laboratory of Psychiatric Neurogenomics, Division of Basic Neuroscience, McLean Hospital, Belmont, MA, 02478, USA. · Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA. · Tianjin Mental Health Center, Tianjin Anding Hospital, 300222, Tianjin, China. · Bio-Organic and Nutritional Products Laboratory, McLean Hospital, Belmont, MA, 02478, USA. · Neuroregeneration Laboratories, McLean Hospital, Belmont, MA, 02478, USA. · Laboratory of Psychiatric Neurogenomics, Division of Basic Neuroscience, McLean Hospital, Belmont, MA, 02478, USA. zhicheng_lin@hms.harvard.edu. ·Neurotherapeutics · Pubmed #27137201.

ABSTRACT: Vesicular monoamine transporter 2 (VMAT2) is responsible for sequestering cytosolically toxic dopamine into intracellular secretory vesicles. Animal genetic studies have suggested that reduced VMAT2 activity contributes to the genetic etiology of Parkinson's disease (PD), but this role has not been established in humans. Based on human genetic association and meta-analysis, we first confirm the human VMAT2 (hVMAT2 or SLC18A2) promoter as a risk factor for PD in both family and unrelated US white people: marker rs363324 at -11.5 kb in the hVMAT2 promoter is reproducibly associated with PD in a cohort of nuclear families (p = 0.04506 in early-onset PD) and 3 unrelated US white people (meta-analysis p = 0.01879). In SH-SY5Y cells, low activity-associated hVMAT2 promoter confers high methylpiperidinopyrazole iodide cytotoxicity, which is likely attributed to functional polymorphisms bound by nuclear proteins. Interestingly, treatments with the dopamine neuron-protecting agent puerarin upregulates the promoter activity in a haplotype- and cell line-dependent manner. These pharmacogenetic findings suggest that hVMAT2 could be a risk factor and imply it as a target of genetic medications for PD.

24 Article [Correlations between constipation and the axial symptoms, related motor symptoms in Parkinson's disease]. 2016

Dai, Yan / Mao, Chengjie / Ding, Mengmeng / Ma, Lijing / Fu, Yunting / Zhang, Huijun / Li, Jie / Liu, Chunfeng. ·Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China. ·Zhonghua Yi Xue Za Zhi · Pubmed #26875708.

ABSTRACT: OBJECTIVE: To investigate the clinical characteristics of Parkinson's Disease (PD) patients with constipation and explore the correlation between constipation and motor symptoms. METHODS: The demographic data of outpatients with PD in our hospital was collected. According to Rome Ⅲ criteria, we evaluated the status of constipation in PD patients. Unified Parkinson's disease rating scale part Ⅲ (UPDRSⅢ), mini-mental state examination (MMSE) were performed in all the included patients. RESULTS: Among the 158 recruited PD patients, 96 (60.8%) patients had constipation. Among these patients, 41(42.7%) patients experienced constipation before motor symptoms. Compared to those without constipation, PD patients with constipation had higher axial scores (6.8±3.4 vs 4.3±2.5, t=-4.887, P=0.000) and gait/postural stability scores (3.9±2.4 vs 2.4±1.5, t=-4.529, P=0.000), higher proportion of axial and gait/postural stability scores in UPDRSⅢ (32%±11% vs 25%±12%, t=-3.485, P=0.001; 18%±9% vs 15%±10%, t=-2.278, P=0.024), more rapid progression of axial and gait/postural stability symptoms (P<0.05). However, there were no differences in other sub-scores and progression of motor symptoms between the two groups (P>0.05). The PD patients with constipation preceding motor symptoms had higher proportion of axial and gait/postural stability scores in UPDRSⅢ (35%±11% vs 30%±10%, t=2.167, P=0.033; 21%±9% vs 16%±8%, t=2.733, P=0.008), indicating these patients may progress more rapidly, meanwhile, they had later onset age, shorter disease duration (P<0.05). Unconditioned Logistic regression showed that axial score was major influencing factor of constipation in PD patients (P=0.000, OR=1.330). CONCLUSIONS: PD patients with constipation have severer axial symptoms, indicating the progression of these patients is relatively rapid, especially those with constipation preceding motor symptoms. It is suggested that axial symptoms and constipation are acted as interactional factors in PD.

25 Article Overexpression of α-synuclein simultaneously increases glutamate NMDA receptor phosphorylation and reduces glucocerebrosidase activity. 2016

Yang, Junfeng / Hertz, Ellen / Zhang, Xiaoqun / Leinartaité, Lina / Lundius, Ebba Gregorsson / Li, Jie / Svenningsson, Per. ·Translational Neuropharmacology, Department of Clinical Neuroscience, Center for Molecular Medicine L8:01, Karolinska Institute, Stockholm 171 76, Sweden; Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300071, China. · Translational Neuropharmacology, Department of Clinical Neuroscience, Center for Molecular Medicine L8:01, Karolinska Institute, Stockholm 171 76, Sweden. · Department of Mental Health Center, Tianjin Medical University, 13 Liulin Road, Tianjin 300222, China. Electronic address: jieli@tmu.edu.cn. · Translational Neuropharmacology, Department of Clinical Neuroscience, Center for Molecular Medicine L8:01, Karolinska Institute, Stockholm 171 76, Sweden. Electronic address: per.svenningsson@ki.se. ·Neurosci Lett · Pubmed #26610904.

ABSTRACT: Progressive accumulation of α-synuclein (α-syn)-containing protein aggregates throughout the nervous system is a pathological hallmark of Parkinson's disease (PD). The mechanisms whereby α-syn exerts neurodegeneration remain to be fully understood. Here we show that overexpression of α-syn in transgenic mice leads to increased phosphorylation of glutamate NMDA receptor (NMDAR) subunits NR1 and NR2B in substantia nigra and striatum as well as reduced glucocerebrosidase (GCase) levels. Similarly, molecular studies performed in mouse N2A cells stably overexpressing human α-syn ((α-syn)N2A) showed that phosphorylation states of the same NMDAR subunits were increased, whereas GCase levels and lysosomal GCase activity were reduced. (α-syn)N2A cells showed an increased sensitivity to neurotoxicity towards 6-hydroxydopamine and NMDA. However, wildtype N2A, but not (α-syn)N2A cells, showed a further reduction in viability when co-incubated with 6-hydroxydopamine and the lysosomal inhibitors NH4Cl and leupeptin, suggesting that α-syn per se perturbs lysosomal functions. NMDA treatment reduced lysosomal GCase activity to the same extent in (α-syn)N2A cells as in wildtype N2A cells, indicating that the α-syn-dependent difference in NMDA neurotoxicity is unrelated to an altered GCase activity. Nevertheless, these data provide molecular evidence that overexpression of α-syn simultaneously induces two potential neurotoxic hits by increasing glutamate NMDA receptor phosphorylation, consistent with increased NMDA receptors functionality, and reducing GCase activity.

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