Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Parkinson Disease: HELP
Articles by Nian Xiong
Based on 27 articles published since 2010
(Why 27 articles?)
||||

Between 2010 and 2020, N. Xiong wrote the following 27 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Multiple pathways for natural product treatment of Parkinson's disease: A mini review. 2019

Li, Jingwen / Long, Xi / Hu, Jichuan / Bi, Juan / Zhou, Ting / Guo, Xingfang / Han, Chao / Huang, Jinsha / Wang, Tao / Xiong, Nian / Lin, Zhicheng. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. · Department of Neurology, People's Hospital of Dongxihu District, Wuhan, Hubei 430040, China. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China; Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China; Department of Neurology, People's Hospital of Dongxihu District, Wuhan, Hubei 430040, China. Electronic address: nianxiong@hust.edu.cn. · Laboratory of Psychiatric Neurogenomics, McLean Hospital, Harvard Medical School, Belmont, MA 02478, United States. Electronic address: zlin@mclean.harvard.edu. ·Phytomedicine · Pubmed #31130327.

ABSTRACT: BACKGROUND: It is established that natural medicines for Parkinson's disease (PD) provide an antioxidant activity in preventing dopaminergic neurons from degeneration. However, the underlying and related molecular details remain poorly understood. METHODS AND AIM: We review published in vitro and rodent studies of natural products in PD models with the aim to identify common molecular pathways contributing to the treatment efficacy. Commonly regulated genes were identified through the systemic literature search and further analyzed from a network perspective. FINDINGS: Approximately thirty different types of natural products have been investigated for their ability to regulate protein density and gene activity in various experimental systems. Most were found to attenuate neurotoxin-induced regulations. Three common PD pathways are involved. The most studied pathway was neuronal development/anti-apoptosis consisting of Bax/Bcl-2, caspases 3/9, and MAPK signaling. Another well studied was anti-inflammation comprising iNOS, nNOS, Nrf2/ARE, cytokines, TNFα, COX2 and MAPK signaling. The third pathway referred to dopamine transmission modulation with upregulated VMAT2, DAT, NURR1 and GDNF levels. To date, HIPK2, a conserved serine/threonine kinase and transcriptional target of Nrf2 in an anti-apoptosis signaling pathway, is the first protein identified as the direct binding target of a natural product (ZMHC). IMPLICATIONS: Natural products may utilize multiple and intercellular pathways at various steps to prevent DA neurons from degeneration. Molecular delineation of the mechanisms of actions is revealing new, perhaps combinational therapeutic approaches to stop the progression of DA degeneration.

2 Review New Perspectives on Roles of Alpha-Synuclein in Parkinson's Disease. 2018

Zhang, Guoxin / Xia, Yun / Wan, Fang / Ma, Kai / Guo, Xingfang / Kou, Liang / Yin, Sijia / Han, Chao / Liu, Ling / Huang, Jinsha / Xiong, Nian / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · Department of Neurology, Anhui Provincial Hospital, The First Affiliated Hospital of Science and Technology of China, Hefei, China. ·Front Aging Neurosci · Pubmed #30524265.

ABSTRACT: Parkinson's disease (PD) is one of the synucleinopathies spectrum of disorders typified by the presence of intraneuronal protein inclusions. It is primarily composed of misfolded and aggregated forms of alpha-synuclein (α-syn), the toxicity of which has been attributed to the transition from an α-helical conformation to a β-sheetrich structure that polymerizes to form toxic oligomers. This could spread and initiate the formation of "LB-like aggregates," by transcellular mechanisms with seeding and subsequent permissive templating. This hypothesis postulates that α-syn is a prion-like pathological agent and responsible for the progression of Parkinson's pathology. Moreover, the involvement of the inflammatory response in PD pathogenesis has been reported on the excessive microglial activation and production of pro-inflammatory cytokines. At last, we describe several treatment approaches that target the pathogenic α-syn protein, especially the oligomers, which are currently being tested in advanced animal experiments or are already in clinical trials. However, there are current challenges with therapies that target α-syn, for example, difficulties in identifying varying α-syn conformations within different individuals as well as both the cost and need of long-duration large trials.

3 Review Weight Loss and Malnutrition in Patients with Parkinson's Disease: Current Knowledge and Future Prospects. 2018

Ma, Kai / Xiong, Nian / Shen, Yan / Han, Chao / Liu, Ling / Zhang, Guoxin / Wang, Luxi / Guo, Shiyi / Guo, Xingfang / Xia, Yun / Wan, Fang / Huang, Jinsha / Lin, Zhicheng / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · Department of Neurology, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China. · Department of Psychiatry, Harvard Medical School, Division of Basic Neuroscience, and Mailman Neuroscience Research Center, McLean Hospital, Belmont, MA, United States. ·Front Aging Neurosci · Pubmed #29403371.

ABSTRACT: Parkinson's Disease (PD) is currently considered a systemic neurodegenerative disease manifested with not only motor but also non-motor symptoms. In particular, weight loss and malnutrition, a set of frequently neglected non-motor symptoms, are indeed negatively associated with the life quality of PD patients. Moreover, comorbidity of weight loss and malnutrition may impact disease progression, giving rise to dyskinesia, cognitive decline and orthostatic hypotension, and even resulting in disability and mortality. Nevertheless, the underlying mechanism of weight loss and malnutrition in PD remains obscure and possibly involving multitudinous, exogenous or endogenous, factors. What is more, there still does not exist any weight loss and malnutrition appraision standards and management strategies. Given this, here in this review, we elaborate the weight loss and malnutrition study status in PD and summarize potential determinants and mechanisms as well. In conclusion, we present current knowledge and future prospects of weight loss and malnutrition in the context of PD, aiming to appeal clinicians and researchers to pay a closer attention to this phenomena and enable better management and therapeutic strategies in future clinical practice.

4 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.

5 Review The implication of neuronimmunoendocrine (NIE) modulatory network in the pathophysiologic process of Parkinson's disease. 2017

Shen, Yan / Guo, Xingfang / Han, Chao / Wan, Fang / Ma, Kai / Guo, Shiyi / Wang, Luxi / Xia, Yun / Liu, Ling / Lin, Zhicheng / Huang, Jinsha / Xiong, Nian / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China. · Division of Alcohol and Drug Abuse, Department of Psychiatry, and Mailman Neuroscience Research Center, McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China. wangtaowh@hust.edu.cn. ·Cell Mol Life Sci · Pubmed #28623510.

ABSTRACT: Parkinson's disease (PD) is a progressive neurodegenerative disorder implicitly marked by the substantia nigra dopaminergic neuron degeneration and explicitly characterized by the motor and non-motor symptom complexes. Apart from the nigrostriatal dopamine depletion, the immune and endocrine study findings are also frequently reported, which, in fact, have helped to broaden the symptom spectrum and better explain the pathogenesis and progression of PD. Nevertheless, based on the neural, immune, and endocrine findings presented above, it is still difficult to fully recapitulate the pathophysiologic process of PD. Therefore, here, in this review, we have proposed the neuroimmunoendocrine (NIE) modulatory network in PD, aiming to achieve a more comprehensive interpretation of the pathogenesis and progression of this disease. As a matter of fact, in addition to the classical motor symptoms, NIE modulatory network can also underlie the non-motor symptoms such as gastrointestinal, neuropsychiatric, circadian rhythm, and sleep disorders in PD. Moreover, the dopamine (DA)-melatonin imbalance in the retino-diencephalic/mesencephalic-pineal axis also provides an alternative explanation for the motor complications in the process of DA replacement therapy. In conclusion, the NIE network can be expected to deepen our understanding and facilitate the multi-dimensional management and therapy of PD in future clinical practice.

6 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.

7 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.

8 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.

9 Review Effectiveness of traditional Chinese medicine as an adjunct therapy for Parkinson's disease: a systematic review and meta-analysis. 2015

Zhang, Guoxin / Xiong, Nian / Zhang, Zhentao / Liu, Ling / Huang, Jinsha / Yang, Jiaolong / Wu, Jing / Lin, Zhicheng / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. · Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. · Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. · Department of Psychiatry, McLean Hospital, Harvard Medical School, Division of Alcohol and Drug Abuse, and Mailman Neuroscience Research Center, Belmont, Massachusetts, United States of America; Harvard Neuro Discovery Center, Boston, Massachusetts, United States of America. ·PLoS One · Pubmed #25756963.

ABSTRACT: BACKGROUND: Idiopathic Parkinson disease (PD) is a common neurodegenerative disease that seriously hinders limb activities and affects patients' lives. We performed a meta-analysis aiming to systematically review and quantitatively synthesize the efficacy and safety of traditional Chinese medicine (TCM) as an adjunct therapy for clinical PD patients. METHODS: An electronic search was conducted in PubMed, Cochrane Controlled Trials Register, China National Knowledge Infrastructure, Chinese Scientific Journals Database and Wanfang data to identify randomized trials evaluating TCM adjuvant therapy versus conventional treatment. The change from baseline of the Unified Parkinson's Disease Rating Scale score (UPDRS) was used to estimate the effectiveness of the therapies. RESULTS: Twenty-seven articles involving 2314 patients from 1999 to 2013 were included. Potentially marked improvements were shown in UPDRS I (SMD 0.68, 95%CI 0.38, 0.98), II (WMD 2.41, 95%CI 1.66, 2.62), III (WMD 2.45, 95%CI 2.03, 2.86), IV (WMD 0.32, 95%CI 0.15, 049) and I-IV total scores (WMD 6.18, 95%CI 5.06, 7.31) in patients with TCM plus dopamine replacement therapy (DRT) compared to DRT alone. Acupuncture add-on therapy was markedly beneficial for improving the UPDRS I-IV total score of PD patients (WMD 10.96, 95%CI 5.85, 16.07). However, TCM monotherapy did not improve the score. The effectiveness seemed to be more obvious in PD patients with longer adjunct durations. TCM adjuvant therapy was generally safe and well tolerated. CONCLUSIONS: Although the data were limited by methodological flaws in many studies, the evidence indicates the potential superiority of TCM as an alternative therapeutic for PD treatment and justifies further high-quality studies.

10 Review Impulsive and compulsive behaviors in Parkinson's disease. 2014

Zhang, Guoxin / Zhang, Zhentao / Liu, Ling / Yang, Jiaolong / Huang, Jinsha / Xiong, Nian / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China. · Department of Neurology, Renmin Hospital of Wuhan University , Wuhan , China. ·Front Aging Neurosci · Pubmed #25452726.

ABSTRACT: BACKGROUND: Impulsive and compulsive behaviors (ICBs) are a heterogeneous group of conditions that may be caused by long-term dopaminergic replacement therapy (DRT) of Parkinson's disease (PD). The spectrum of ICBs includes dopamine dysregulation syndrome (DDS), punding, and impulse control disorders (ICDs). CONTENTS: We made a detailed review regarding the epidemiology, pathology, clinical characteristics, risk factors, diagnosis as well as treatment of ICBs. RESULTS: The prevalence of ICBs in PD patients is approximately 3-4% for DDS, 0.34-4.2% for punding, and 6-14% for ICDs, with higher prevalence in Western populations than in Asian. Those who take high dose of levodopa are more prone to have DDS, whereas, ICDs are markedly associated with dopamine agonists. Different subtypes of ICBs share many risk factors such as male gender, higher levodopa equivalent daily dose, younger age at PD onset, history of alcoholism, impulsive, or novelty-seeking personality. The Questionnaire for Impulsive-Compulsive Disorder in Parkinson's Disease-Rating Scale seems to be a rather efficacious instrument to obtain relevant information from patients and caregivers. Treatment of ICBs is still a great challenge for clinicians. Readjustment of DRT remains the primary method. Atypical antipsychotics, antidepressants, amantadine, and psychosocial interventions are also prescribed in controlling episodes of psychosis caused by compulsive DRT, but attention should be drawn to balance ICBs symptoms and motor disorders. Moreover, deep brain stimulation of the subthalamic nucleus might be a potential method in controlling ICBs. CONCLUSION: The exact pathophysiological mechanisms of ICBs in PD remains poorly understood. Further researches are needed not only to study the pathogenesis, prevalence, features, and risk factors of ICBs, but to find efficacious therapy for patients with these devastating consequences.

11 Review Mitochondrial complex I inhibitor rotenone-induced toxicity and its potential mechanisms in Parkinson's disease models. 2012

Xiong, Nian / Long, Xi / Xiong, Jing / Jia, Min / Chen, Chunnuan / Huang, Jinsha / Ghoorah, Devina / Kong, Xiangquan / Lin, Zhicheng / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430022, China. ·Crit Rev Toxicol · Pubmed #22574684.

ABSTRACT: The etiology of Parkinson's disease (PD) is attributed to both environmental and genetic factors. The development of PD reportedly involves mitochondrial impairment, oxidative stress, α-synuclein aggregation, dysfunctional protein degradation, glutamate toxicity, calcium overloading, inflammation and loss of neurotrophic factors. Based on a link between mitochondrial dysfunction and pesticide exposure, many laboratories, including ours, have recently developed parkinsonian models by utilization of rotenone, a well-known mitochondrial complex I inhibitor. Rotenone models for PD appear to mimic most clinical features of idiopathic PD and recapitulate the slow and progressive loss of dopaminergic (DA) neurons and the Lewy body formation in the nigral-striatal system. Notably, potential human parkinsonian pathogenetic and pathophysiological mechanisms have been revealed through these models. In this review, we summarized various rotenone-based models for PD and discussed the implied etiology of and treatment for 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 Reduced VMAT2 expression exacerbates the hyposmia in the MPTP model of Parkinson's disease. 2019

Ma, Kai / Han, Chao / Zhang, Guoxin / Guo, Xingfang / Xia, Yun / Wan, Fang / Yin, Sijia / Kou, Liang / Liu, Ling / Huang, Jinsha / Xiong, Nian / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. · Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, PR China. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address: wangtaowh@hust.edu.cn. ·Biochem Biophys Res Commun · Pubmed #30954223.

ABSTRACT: Hyposmia occurs during the prodromal phase of Parkinson's disease (PD), while the underlying mechanisms remain unclear. Discussed are altered dopamine content and impairment of neurogenesis of olfactory bulbs (OB), which has been suggested to be linked to olfactory dysfunction. Given that mouse with reduced vesicular monoamine transporter 2 (VMAT2) expression is now deemed as a relatively new PD animal model simulating motor and nonmotor symptoms, it may provide a new insight into investigating the mechanisms of hyposmia in the context of PD. In this study, we examined the effect of subacute administration of MPTP on mice with a reduced expression of VMAT2, focusing on the histopathological and biochemical alterations, specifically, TH expression level, dopamine content as well as neurogenesis in OB. Interestingly, mice with a reduced VMAT2 expression displayed more obvious olfactory impairment in response to MPTP administration accompanied by markedly decreased dopaminergic interneurons in OB. Furthermore, neurogenesis in OB was also further impaired after MPTP due to reduced VMAT2 expression. We therefore demonstrated that reduced expression of VMAT2 contributed to the impairment of hyposmia, pathologically, the degeneration of extranigral systems and reduced neurogenesis might be the underlying mechanisms.

14 Article Hydralazine Protects Nigrostriatal Dopaminergic Neurons From MPP 2019

Guo, Xingfang / Han, Chao / Ma, Kai / Xia, Yun / Wan, Fang / Yin, Sijia / Kou, Liang / Sun, Yadi / Wu, Jiawei / Hu, Junjie / Huang, Jinsha / Xiong, Nian / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · Department of Neurology, The First Affiliated Hospital of USTC and Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. ·Front Neurol · Pubmed #30949126.

ABSTRACT: Although the pathogenic mechanisms of Parkinson's disease (PD) remain unclear, ample empirical evidence suggests that oxidative stress is involved in the pathogenesis of this disease. The nuclear factor E2-related factor 2 (Nrf2) is known to activate several antioxidant response element (ARE)-driven antioxidative genes that prevents oxidative stress

15 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.

16 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.

17 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.

18 Article Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration. 2016

Xiong, Jing / Zhang, Xiaowei / Huang, Jinsha / Chen, Chunnuan / Chen, Zhenzhen / Liu, Ling / Zhang, Guoxin / Yang, Jiaolong / Zhang, Zhentao / Zhang, Zhaohui / Lin, Zhicheng / 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, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China. · Department of Neurology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China. · Department of Psychiatry, Harvard Medical School; Division of Alcohol and Drug Abuse, and Mailman Neuroscience Research Center, McLean Hospital, Belmont, MA, 02478, USA. · Harvard NeuroDiscovery Center, Boston, MA, 02114, USA. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, China. nianxiongtjmu@gmail.com. · 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 #25575680.

ABSTRACT: Fenpropathrin is one of the widely used pyrethroids in agriculture and household and also reported to have neurotoxic effects in rodent models. In our Parkinson's disease (PD) clinic, there was a unique patient with a history of daily exposure to fenpropathrin for 6 months prior to developing Parkinsonian symptoms progressively. Since whether fenpropathrin is related to any dopaminergic degeneration was unknown, we aimed in this study to evaluate the neurotoxic effects of fenpropathrin on the dopaminergic system and associated mechanisms in vitro and in vivo. In cultured SH-SY5Y cells, fenpropathrin caused cell death, reactive oxygen species generation, Lewy body-associated proteins aggregation, and Lewy body-like intracytoplasmic inclusions formation. In rodent animals, two different injections of fenpropathrin were used for administrations, intraperitoneal (i.p), or stereotaxical (ST). The rats exhibited lower number of pokes 60 days after first i.p injection, while the rats in ST group showed a significant upregulation of apomorphine-evoked rotations 60 days after first injection. Decreased tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT2) immunoreactivity, while increased dopamine transporter (DAT) immunoreactivity were observed in rats of either i.p or ST group 60 days after the last exposure to fenpropathrin. However, the number of TH-positive cells in the substantia nigra was more reduced 120 days after the first i.p injection than those of 60 days. Our data demonstrated that exposure to fenpropathrin could mimic the pathologic and pathogenetic features of PD especially in late onset cases. These results imply fenpropathrin as a DA neurotoxin and a possible environmental risk factor for PD.

19 Article Genetic variants in GAPDH confer susceptibility to sporadic Parkinson's disease in a Chinese Han population. 2015

Liu, Ling / Xiong, Nian / Zhang, Ping / Chen, Chunnuan / Huang, Jinsha / Zhang, Guoxin / Xu, Xiaoyun / Shen, Yan / Lin, Zhicheng / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. · Department of Neurology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. · Department of Neurology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China. · Department of Psychiatry and Harvard NeuroDiscovery Center, Harvard Medical School and Laboratory of Psychiatric Neurogenomics, Division of Alcohol and Drug Abuse, McLean Hospital, Belmont, MA, United States of America. ·PLoS One · Pubmed #26258539.

ABSTRACT: BACKGROUND: Accumulating evidence has demonstrated that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a part of Lewy body inclusions and involves the pathogenesis of Parkinson's disease (PD). However, it remains unknown whether or not genetic variation at the GAPDH locus contributes to the risk for PD. METHODS: A total of 302 sporadic PD patients and 377 control subjects were recruited in our study for assessing two single nucleotide polymorphisms (rs3741918 and rs1060619) in the GAPDH gene. Both allelic association and additive models were used to analyze association between GAPDH variants and risk for PD. RESULTS: Both polymorphisms were significantly associated with risk for PD after correction by Bonferroni multiple testing. The minor allele of rs3741918 was associated with decreased risk of sporadic PD (allelic contrast, OR = 0.74, 95% CI: 0.59-0.93, corrected P = 0.028; additive model, OR = 0.73, 95% CI: 0.58-0.92, corrected P = 0.018). While for the rs1060619 locus, the minor allele conferred increased risk for PD (allelic contrast, OR = 1.41, 95% CI: 1.14-1.75, corrected P = 0.007; additive model, OR = 1.43, 95% CI: 1.15-1.79, corrected P = 0.002). CONCLUSION: Our study indicates that GAPDH variants confer susceptibility to sporadic PD in a Chinese Han population, which is consistent with the role of GAPDH protein in neuronal apoptosis. To our knowledge, this is the first study of genetic association between GAPDH locus and risk for PD in the Chinese population.

20 Article Puerarin protects dopaminergic neurons in Parkinson's disease models. 2014

Zhang, X / Xiong, J / Liu, S / Wang, L / Huang, J / Liu, L / Yang, J / Zhang, G / Guo, K / Zhang, Z / Wu, P / Wang, D / Lin, Z / Xiong, N / Wang, T. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430022, China. · Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China. · Hefeng Central Hospital, Hefeng, Enshi, Hubei 445800, China. · Department of Psychiatry, Harvard Medical School, Division of Alcohol and Drug Abuse, and Mailman Neuroscience Research Center, McLean Hospital, Belmont, MA 02478, USA; Harvard NeuroDiscovery Center, Boston, MA 02114, USA. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430022, China. Electronic address: nianxiongtjmu@gmail.com. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430022, China. Electronic address: wangtaowh@yahoo.cn. ·Neuroscience · Pubmed #25218963.

ABSTRACT: It has been acknowledged that oxidative stress, resulting in the apoptosis of dopaminergic neurons, is a key mechanism in the pathogenesis of Parkinson's disease (PD). Puerarin, extracted from the root of pueraria lobata, has been clinically used for ischemic heart disease and cerebrovascular diseases as an oxygen free radical scavenger. In this study, we aimed to explore the effect of puerarin on dopaminergic cell degeneration in vitro and in vivo and its possible underlying mechanisms. In SH-SY5Y cells, the reduction of cell viability, apoptosis rate and average DCFH-DA fluorescence intensity of puerarin-treated (0, 10, 50, 100 and 150 μM) cells were significantly lower than control group. In rotenone-based rodent models, puerarin treatment for 7 days ameliorated apomorphine-induced rotations significantly in Pue-50 and Pue-100 group by 45.65% and 53.06% in the first week, by 44.60% and 48.45% in the second week. Moreover, compared to control group, puerarin increased tyrosine hydroxylase (TH) expression in the substantia nigra by 85.52% and 84.26% in Pue-50 group and Pue-100 group, and upregulated the vesicular monoamine transporter 2 (VMAT2) by 41.24% in Pue-50 group and 35.20% in Pue-100 group, and decreased ubiquitin expression by 47.55% in Pue-50 group and 69.15% in Pue-100 group. These data indicated that puerarin alleviated the oxidative stress and apoptosis in a PD cellular model, protected the dopaminergic neurons against rotenone toxicity and decreased the abnormal protein overexpressing in PD animal models. These findings suggest that puerarin may develop into a neuroprotective alternative for patients with PD.

21 Article Proliferating cell nuclear antigen binds DNA polymerase-β and mediates 1-methyl-4-phenylpyridinium-induced neuronal death. 2014

Zhang, Zhentao / Zhang, Zhaohui / Wang, Hongcai / Zhang, Guoxin / Hu, Dan / Xiong, Jing / Xiong, Nian / Wang, Tao / Cao, Xuebing / Mao, Ling. ·Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ·PLoS One · Pubmed #25184665.

ABSTRACT: The mechanisms leading to dopaminergic neuronal loss in the substantia nigra of patients with Parkinson disease (PD) remain poorly understood. We recently reported that aberrant DNA replication mediated by DNA polymerase-β (DNA pol-β) plays a causal role in the death of postmitotic neurons in an in vitro model of PD. In the present study, we show that both proliferating cell nuclear antigen (PCNA) and DNA pol-β are required for MPP(+)-induced neuronal death. PCNA binds to the catalytic domain of DNA pol-β in MPP(+)-treated neurons and in post-mortem brain tissues of PD patients. The PCNA-DNA pol-β complex is loaded into DNA replication forks and mediates DNA replication in postmitotic neurons. The aberrant DNA replication mediated by the PCNA-DNA pol-β complex induces p53-dependent neuronal cell death. Our results indicate that the interaction of PCNA and DNA pol-β contributes to neuronal death in PD.

22 Article Non-SMC condensin I complex, subunit D2 gene polymorphisms are associated with Parkinson's disease: a Han Chinese study. 2014

Zhang, Ping / Liu, Ling / Huang, Jinsha / Shao, Liang / Wang, Hongcai / Xiong, Nian / Wang, Tao. ·a Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430022, Wuhan, China. ·Genome · Pubmed #25166511.

ABSTRACT: Previous studies have indicated that non-SMC condensin I complex, subunit D2 (NCAPD2), an important protein in chromosome condensation, gene polymorphisms are associated with Alzheimer's disease. But no study has shown the relationship between NCAPD2 polymorphisms and Parkinson's disease. Here, we conducted a case-control study to investigate the relationship between NCAPD2 polymorphisms and the risk of Parkinson's disease in a Han Chinese population. Two single nuclear polymorphisms (SNPs) of NCAPD2 (rs7311174 and rs2072374) showed significant p values (p = 0.046 and p = 0.043, respectively) in 265 patients and 267 controls. Further analysis showed an effect of age and gender on the relationship between the two SNPs and the risk for Parkinson's disease. The A allele of rs7311174 and the T allele of rs2072374 were protective in the male patients (p = 0.016 and p = 0.019, respectively). The frequencies of the T allele of rs7311174 and the C allele of rs2072374 were significantly associated with late-onset Parkinson's disease (p = 0.048 and p = 0.044, respectively). This research demonstrates a positive relationship between the NCAPD2 gene and the risk for Parkinson's disease in a Han Chinese population and provides a potential genetic marker for sporadic Parkinson's disease.

23 Article MAPT rs242562 and GSK3B rs334558 are associated with Parkinson's Disease in central China. 2014

Yu, Lan / Huang, Jinsha / Zhai, Desheng / Liu, Ling / Guo, Kexin / Long, Xi / Xiong, Jing / Zhang, Zhentao / Wang, Youpei / Zhao, Ying / Wu, Ping / Wang, Dingan / Lin, Zhicheng / Wu, Jing / 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. nianxiongtjmu@gmail.com. ·BMC Neurosci · Pubmed #24779391.

ABSTRACT: BACKGROUND: Microtubule-associated protein tau (MAPT) is a neuronal protein involved in the pathogenesis of several neurodegenerative diseases including Parkinson's Disease (PD). Glycogen synthase kinase 3 beta (GSK3B) catalyzes phosphorylation in multiple sites of tau protein. However, whether or not there is any association between the GSK3B gene alteration, MAPT haplotype and PD remains unexplored in Chinese population, especially in central Chinese population. RESULTS: Here, we aimed at studying the effect of MAPT rs242562 and GSK3B rs334558 on the risk of PD by performing a case-control association study in central China. Our data showed that all PD patients and controls were of MAPT H1/H1 diplotype in our study, thus confirming that the distribution of the MAPT H1 haplotype is common in China. GG genotype of MAPT rs242562 serves protection effect on PD risk in central Chinese population, while genotype of GSK3B rs334558 showed no difference between PD patients and controls. CONCLUSIONS: We conclude that the MAPT rs242562 is associated with PD in central China in the background of MAPT H1/H1 diplotype. The GG genotype of rs242562 displays protection against PD in subgroup with GSK3B rs334558 T carrier.

24 Article bFGF promotes the differentiation and effectiveness of human bone marrow mesenchymal stem cells in a rotenone model for Parkinson's disease. 2013

Xiong, Nian / Yang, Hecheng / Liu, Ling / Xiong, Jing / Zhang, Zhaowen / Zhang, Xiaowei / Jia, Min / Huang, Jinsha / Zhang, Zhentao / Mohamed, Asrah A / Lin, Zhicheng / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430022, China. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430022, China; Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China. · Department of Psychiatry, Harvard Medical School, USA; Division of Alcohol and Drug Abuse, and Mailman Neuroscience Research Center, McLean Hospital, Belmont, MA 02478, USA; Harvard NeuroDiscovery Center, Boston, MA 02114, USA. · Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430022, China. Electronic address: wangtaowh@yahoo.cn. ·Environ Toxicol Pharmacol · Pubmed #23770451.

ABSTRACT: Previous studies have shown that bone marrow mesenchymal stem cells (BMSCs) engraftment could alleviate motor dysfunction in parkinsonian animal models, but with limited efficacy and few engrafted cells surviving. On the other side, basic fibroblast growth factor (bFGF) reportedly displays many effects including neuroprotection and promoting multipotent cells to expand and differentiate. In this study, we assessed whether a combination of bFGF and human BMSCs (HBMSCs) therapy could enhance the treatment effectiveness in Parkinson's disease (PD) rat models. Specifically, bFGF promoted HBMSCs to transdifferentiate toward neural-like lineages in vitro. In addition, HBMSCs transplantation alleviated the motor functional asymmetry, as well as prevented dopaminergic neuron loss in a PD model, while bFGF administration enhances its neurodifferentiation capacity and therapeutic effect. In conclusion, optimizing culture condition like supplementation of bFGF could significantly improve the output of HBMSCs in vitro, and HBMSCs transplantation with bFGF might represent an improved transplantation approach for PD.

25 Article Glucocerebrosidase L444P mutation confers genetic risk for Parkinson's disease in central China. 2012

Wang, Youpei / Liu, Ling / Xiong, Jing / Zhang, Xiaowei / Chen, Zhenzhen / Yu, Lan / Chen, Chunnuan / Huang, Jinsha / Zhang, Zhentao / Mohmed, Asrah A / Lin, Zhicheng / Xiong, Nian / Wang, Tao. ·Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, 430022, China. ·Behav Brain Funct · Pubmed #23227814.

ABSTRACT: BACKGROUND: Mutations of the glucocerebrosidase (GBA) gene have reportedly been associated with Parkinson disease (PD) in various ethnic populations such as Singaporean, Japanese, Formosan, Canadian, American, Portuguese, Greek, Brazilian, British, Italian, Ashkenazi Jewish, southern and southwestern Chinese. The purpose of this study is to determine in central China whether or not the reported GBA mutations remain associated with PD. METHODS: In this project, we conducted a controlled study in a cohort of 208 central Chinese PD patients and 298 controls for three known GBA mutations (L444P, N370S and R120W). RESULTS: Our data reveals a significantly higher frequency of L444P mutation in GBA gene of PD cases (3.4%) compared with the controls (0.3%) (P = 0.007, OR = 10.34, 95% CI = 1.26 - 84.71). Specifically, the frequency of L444P mutation was higher in the late onset PD (LOPD) cases compared with that in control subjects. The N370S and R120W mutations were detected in neither the PD group nor the control subjects. CONCLUSIONS: Our observations demonstrated that the GBA L444P mutation confers genetic risk for PD, especially LOPD, among the population in the central China area.

Next