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Parkinson Disease: HELP
Articles from Tokyo
Based on 677 articles published since 2010
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These are the 677 published articles about Parkinson Disease that originated from Tokyo during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14 · 15 · 16 · 17 · 18 · 19 · 20
1 Editorial Behavioural and Cognitive Changes in Lewy Body Dementias. 2018

Kung, Woon-Man / Ho, Ying-Jui / Yoshizawa, Hiroshi / Matsuo, Shinro / Wei, Cheng-Yu. ·Department of Exercise and Health Promotion, College of Education, Chinese Culture University, Taipei, Taiwan. · Division of Neurosurgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan. · Department of Surgery, School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan. · Department of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan. · Department of Neurology, Neurological Institute, Tokyo Women's Medical University, Kawadacho, Shinjuku, Tokyo, Japan. · Department of Nuclear Medicine, Kanazawa University Hospital, Takaramachi, Kanazawa, Japan. · Department of Neurology, Chang Bing Show Chwan Memorial Hospital, Changhua County, Taiwan. ·Behav Neurol · Pubmed #30534208.

ABSTRACT: -- No abstract --

2 Editorial Biomedical devices go wild. 2018

Rogers, John / Malliaras, George / Someya, Takao. ·John Rogers, Northwestern University, Evanston, IL 60208, USA. Email: jrogers@northwestern.edu. · George Malliaras, University of Cambridge, Cambridge, UK. Email: gm603@cam.ac.uk. · Takao Someya, University of Tokyo, Tokyo, Japan. Email: someya@ee.t.u-tokyo.ac.jp. ·Sci Adv · Pubmed #30255157.

ABSTRACT: -- No abstract --

3 Editorial Editorial and introduction: Behavioral aspects of Parkinson's disease. 2017

Friedman, Joseph H / Bhidayasiri, Roongroj / Truong, Daniel D. ·Butler Hospital, Department of Neurology, Alpert Medical School of Brown University, RI, USA. · Chulalongkorn Center of Excellence for Parkinson's Disease & Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand; Department of Rehabilitation Medicine, Juntendo University, Tokyo, Japan. Electronic address: rbh@chulapd.org. · Truong Neuroscience Institute, Parkinson's and Movement Disorders Institute, Orange Coast Memorial Medical Center, Fountain Valley, CA, USA. ·J Neurol Sci · Pubmed #28087061.

ABSTRACT: -- No abstract --

4 Editorial Nonmotor symptoms in Parkinson's disease: are we still waiting for the honeymoon? 2016

Colosimo, C / Bhidayasiri, R. ·Department of Neurology, Santa Maria University Hospital, Terni, Italy. carlo.colosimo@uniroma1.it. · Department of Medicine, Faculty of Medicine, Chulalongkorn Center of Excellence for Parkinson's Disease and Related Disorders, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. · Department of Rehabilitation Medicine, Juntendo University, Tokyo, Japan. ·Eur J Neurol · Pubmed #27611181.

ABSTRACT: -- No abstract --

5 Editorial What is NODDI and what is its role in Parkinson's assessment? 2016

Kamagata, Koji / Hatano, Taku / Aoki, Shigeki. ·b Department of Radiology , Juntendo University Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan. · a Department of Neurology , Juntendo University Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan. ·Expert Rev Neurother · Pubmed #26777076.

ABSTRACT: -- No abstract --

6 Editorial Familial Parkinson's disease/parkinsonism. 2015

Tomiyama, Hiroyuki / Lesage, Suzanne / Tan, Eng-King / Jeon, Beom S. ·Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. · Sorbonne Universités, UPMC Université Paris 6 UMRS 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. · Department of Neurology, Singapore General Hospital and Neuroscience & Behavioral Disorders Program, Duke-NUS Graduate Medical School, National Neuroscience Institute, Singapore. · Department of Neurology, Seoul National University Hospital, Seoul, Republic of Korea. ·Biomed Res Int · Pubmed #25961036.

ABSTRACT: -- No abstract --

7 Review [Indication for Deep Brain Stimulation]. 2019

Shimo, Yasushi / Umemura, Atsushi / Hattori, Nobutaka. ·Department of Research and Therapeutics for Movement Disorders, Juntendo University Department of Neurology, Juntendo University Graduate School of Medicine. ·Brain Nerve · Pubmed #31346145.

ABSTRACT: Various methods for the management of motor fluctuation in Parkinson's disease have been developed. Among them, deep brain stimulation (DBS) is an important therapeutic option that has been proved to be effective. However, the indications and timing of induction therapy are controversial. When contemplating therapy, it is important to consider not only the motor function but also the specific disease course and psychiatric aspects, of each patient.

8 Review [Modeling Familial Parkinson's Disease Using Patient-specific Induced Pluripotent Stem Cells]. 2019

Tabata, Yoshikuni / Okano, Hideyuki. ·Department of Physiology, Keio University School of Medicine. ·Brain Nerve · Pubmed #31346144.

ABSTRACT: Parkinson's disease (PD), a common neurodegenerative disorder, is characterized by selective degeneration of dopaminergic neurons in the substantia nigra. There is no effective treatment to delay or halt the progression of PD. The establishment of disease models, based on human biology, is therefore important for developing effective disease-modifying therapies. The recent progress of human induced pluripotent stem cell-associated technologies provides an opportunity to understand disease etiology, discover new drugs, and develop novel therapeutic interventions.

9 Review [Diagnosis and Treatment of Cognitive Impairment in Parkinson's Disease]. 2019

Shiraishi, Tomotaka / Murakami, Hidetomo / Iguchi, Yasuyuki. ·Department of Neurology, The Jikei University School of Medicine. ·Brain Nerve · Pubmed #31346143.

ABSTRACT: Parkinson's disease (PD) patients can present with cognitive impairment, such as deficits in attention and memory processes, visual perception, executive function and social cognition. These dysfunctions negatively affect the activities of daily living and outcome of patients. Some of the risk factors, pathological background and etiology of cognitive dysfunction in PD with dementia (PDD) have been determined. Treatments for such dysfunctions are attracting much attention. Some medications, such as donepezil, rivastigmine, and memantine, have shown to improve motor and/or cognitive functions. Cognitive impairment and motor symptoms in PD can be treated concurrently. Therefore, the correlation between motor and cognitive function should be considered when treating PD.

10 Review Lipids as 2019

Ikenaka, Kensuke / Suzuki, Mari / Mochizuki, Hideki / Nagai, Yoshitaka. ·Department of Neurology, Graduate School of Medicine, Osaka University, Osaka, Japan. · Department of Neurotherapeutics, Graduate School of Medicine, Osaka University, Osaka, Japan. · Diabetic Neuropathy Project, Department of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. ·Front Neurosci · Pubmed #31333408.

ABSTRACT: Aggregation of α-synuclein (αSyn) plays a central role in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Lewy bodies (LBs) and Lewy neurites, which consist mainly of aggregated αSyn, are widely observed in the affected regions of patient brains. Except for some familial forms of PD/DLB, most sporadic PD/DLB patients express the wild-type (WT) αSyn protein without any mutations, and the mechanisms as to how WT αSyn gains the propensity to pathologically aggregate still remains unclear. Furthermore, the mechanisms by which the same αSyn protein can cause different synucleinopathies with distinct phenotypes and pathologies, such as PD, DLB, and multiple system atrophy (MSA), still remain largely unknown. Recently, mutations in the

11 Review [Prion-like Propagation of Pathological α-Synuclein in Vivo]. 2019

Masuda-Suzukake, Masami / Hasegawa, Masato. ·Dementia Research Project, Tokyo Metropolitan Institute of Medical Science. ·Yakugaku Zasshi · Pubmed #31257247.

ABSTRACT: α-Synuclein (αS) is the major component of the filamentous inclusions that constitute the defining characteristic of neurodegenerative synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. αS is deposited in a hyperphosphorylated and ubiquitinated form with a β-sheet-rich fibrillar structure in diseased brains. In 2008, some researchers reported that embryonic neurons transplanted into Parkinson's disease brains had Lewy body-like pathologies, suggesting that pathological αS propagates from diseased neurons to young neurons. Subsequently, a growing body of evidence supported the cell-to-cell spread of αS pathologies. Recent studies have revealed that intracerebral injection of insoluble αS into wild-type mice can induce prion-like propagation of phosphorylated αS pathology even 1 month after injection, while injection into αS-knockout mice failed to induce any pathology. We also showed that intracerebral injection of insoluble αS into adult common marmoset brains results in the spreading of abundant αS pathology. These in vivo experiments clearly indicate that insoluble αS has prion-like properties and that it propagates through neural networks. The underlying mechanisms of αS propagation are still poorly understood, but αS propagation model animals could be helpful in elucidating the pathogenetic mechanisms and developing drugs for synucleinopathies.

12 Review The dawn of pirna research in various neuronal disorders. 2019

Wakisaka, Keiko Tsuji / Imai, Yuzuru. ·Department of Research for Parkinson's Disease, and Neurology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan, k-wakisaka@mbn.nifty.com. · Department of Research for Parkinson\'s Disease, and Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan. ·Front Biosci (Landmark Ed) · Pubmed #31136989.

ABSTRACT: Small non-coding PIWI-interacting RNAs (piRNAs) silence the expression of transposable elementsof eukaryotic genomes in germline cells. Additionally, piRNAs regulate chromatin modifications, such as trimethylation of histone H3 lysine 9 (H3K9me3) or DNA methylation. In the past decade, the roles of piRNAs have been characterized in somatic cells, including post-mitotic neurons. More recently, piRNAs have been shown to play important roles in brain functions and various neuronal diseases, including neurodegenerative disorders. In this review, we introduce recent findings showing the potential involvement of piRNAs in the etiology of different neurodegenerative diseases, including

13 Review Twin CHCH Proteins, CHCHD2, and CHCHD10: Key Molecules of Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia. 2019

Imai, Yuzuru / Meng, Hongrui / Shiba-Fukushima, Kahori / Hattori, Nobutaka. ·Department of Research for Parkinson's Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan. yzimai@juntendo.ac.jp. · Department of Treatment and Research in Multiple Sclerosis and Neuro-intractable Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan. yzimai@juntendo.ac.jp. · Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan. hmon@juntendo.ac.jp. · Department of Neurodegenerative and Demented Disorders, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan. kshiba@juntendo.ac.jp. · Department of Research for Parkinson's Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan. nhattori@juntendo.ac.jp. · Department of Treatment and Research in Multiple Sclerosis and Neuro-intractable Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan. nhattori@juntendo.ac.jp. · Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan. nhattori@juntendo.ac.jp. · Department of Neurodegenerative and Demented Disorders, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan. nhattori@juntendo.ac.jp. ·Int J Mol Sci · Pubmed #30791515.

ABSTRACT: Mutations of

14 Review Human tyrosine hydroxylase in Parkinson's disease and in related disorders. 2019

Nagatsu, Toshiharu / Nakashima, Akira / Ichinose, Hiroshi / Kobayashi, Kazuto. ·School of Medicine, Fujita Health University, Toyoake, Aichi, 470-1192, Japan. tnagatsu@fujita-hu.ac.jp. · Department of Physiological Chemistry, School of Medicine, Fujita Health University, Toyoake, Aichi, 470-1192, Japan. · School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan. · Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University, Fukushima, 960-1295, Japan. ·J Neural Transm (Vienna) · Pubmed #29995172.

ABSTRACT: Parkinson's disease (PD) is an aging-related movement disorder mainly caused by a deficiency of neurotransmitter dopamine (DA) in the striatum of the brain and is considered to be due to progressive degeneration of nigro-striatal DA neurons. Most PD is sporadic without family history (sPD), and there are only a few percent of cases of young-onset familial PD (fPD, PARKs) with the chromosomal locations and the genes identified. Tyrosine hydroxylase (TH), tetrahydrobiopterin (BH4)-dependent and iron-containing monooxygenase, catalyzes the conversion of L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA), which is the initial and rate-limiting step in the biosynthesis of catecholamines (DA, noradrenaline, and adrenaline). PD affects specifically TH-containing catecholamine neurons. The most marked neurodegeneration in patients with DA deficiency is observed in the nigro-striatal DA neurons, which contain abundant TH. Accordingly, TH has been speculated to play some important roles in the pathophysiology in PD. However, this decrease in TH is thought to be secondary due to neurodegeneration of DA neurons caused by some as yet unidentified genetic and environmental factors, and thus, TH deficiency may not play a direct role in PD. This manuscript provides an overview of the role of human TH in the pathophysiology of PD, covering the following aspects: (1) structures of the gene and protein of human TH in relation to PD; (2) similarity and dissimilarity between the phenotypes of aging-related sPD and those of young-onset fPD or DOPA-responsive dystonia due to DA deficiency in the striatum with decreased TH activity caused by mutations in either the TH gene or GTP cyclohydrolase I (GCH1) gene; and (3) genetic variants of the TH gene (polymorphisms, rare variants, and mutations) in PD, as discovered recently by advanced genome analysis.

15 Review MDSGene: Closing Data Gaps in Genotype-Phenotype Correlations of Monogenic Parkinson's Disease. 2018

Klein, Christine / Hattori, Nobutaka / Marras, Connie. ·Institute of Neurogenetics, University of Luebeck, Luebeck, Germany. · Edmond J Safra Program in Parkinson's disease, University Health Network, University of Toronto, Canada. · Department of Neurology, Juntendo University, Bunkyo, Tokyo, Japan. ·J Parkinsons Dis · Pubmed #30584170.

ABSTRACT: Given the rapidly increasing number of reported movement disorder genes and clinical-genetic desciptions of mutation carriers, the International Parkinson's Disease and Movement Disorder Society Gene Database (MDSGene) initiative has been launched in 2016 and grown to become a large international project (http://www.mdsgene.org). MDSGene currently contains >1150 variants described in ∼5700 movement disorder patients in almost 1000 publications including monogenic forms of PD clinically resembling idiopathic (PARK-PINK1, PARK-Parkin, PARK-DJ-1, PARK-SNCA, PARK-VPS35, PARK-LRRK2), as well as of atypical PD (PARK-SYNJ1, PARK-DNAJC6, PARK-ATP13A2, PARK-FBXO7). Inclusion of genes is based on standardized published criteria for determining causation. Clinical and genetic information can be filtered according to demographic, clinical or genetic criteria and summary statistics are automatically generated by the MDSGene online tool. Despite MDSGene's novel approach and features, it also faces several challenges: i) The criteria for designating genes as causative will require further refinement, as well as time and support to replace the faulty list of 'PARKs'. ii) MDSGene has uncovered extensive clinical data gaps. iii) The quickly growing body of clinical and genetic data require a large number of experts worldwide posing logistic challenges. iv) MDSGene currently captures published data only, i.e., a small fraction of the available information on monogenic PD available. Thus, an important future aim is to extend MDSGene to unpublished cases in order to provide the broad data base to the PD community that is necessary to comprehensively inform genetic counseling, therapeutic approaches and clinical trials, as well as basic and clinical research studies in monogenic PD.

16 Review [Impairment of Cross-modality: A New Cognitive Dysfunction in Parkinson's Disease]. 2018

Honma, Motoyasu. ·Department of Physiology, Kyorin University School of Medicine. ·Brain Nerve · Pubmed #30416108.

ABSTRACT: It is known that Parkinson's disease impairs various cognitive functions including olfaction. However, until recently it was unclear whether Parkinson's disease also affects cross-modal function of vision and olfaction. A recent study showed that odor evaluation in patients with Parkinson's disease is unaffected by visual information, while healthy controls overestimated smell, when sniffing odorless liquid while viewing pleasant or unpleasant visual cues. Dopamine transporter deficit in the striatum, in particular in the posterior putamen, correlated with the limited visual effect in patients with Parkinson's disease. The findings suggest that Parkinson's disease impairs cross-modal function of vision and olfaction due to posterior putamen deficit. This review discusses that the cross-modal dysfunction may serve as the basis of novel precursor assessment of Parkinson's disease.

17 Review Regulation of membrane dynamics by Parkinson's disease-associated genes. 2018

Inoshita, Tsuyoshi / Cui, Changxu / Hattori, Nobutaka / Imai, Yuzuru. ·Department of Research for Parkinson's Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan. yzimai@juntendo.ac.jp. ·J Genet · Pubmed #30027905.

ABSTRACT: Parkinson's disease (PD), the second most common neurodegenerative disease after Alzheimer's disease, develops sporadically, and its cause is unknown. However, 5-10% of PD cases are inherited as monogenic diseases, which provides a chance to understand the molecular mechanisms underlying neurodegeneration. Over 20 causative genes have already been identified and are being characterized. These PD-associated genes are broadly classified into two groups: genes involved in mitochondrial functions and genes related to membrane dynamics such as intracellular vesicle transport and the lysosomal pathway. In this review, we summarize the latest findings on the mechanism by which members of the latter group of PD-associated genes regulate membrane dynamics, and we discuss how mutations of these genes lead to dopaminergic neurodegeneration.

18 Review Association Between Autophagy and Neurodegenerative Diseases. 2018

Fujikake, Nobuhiro / Shin, Minkyoung / Shimizu, Shigeomi. ·Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. ·Front Neurosci · Pubmed #29872373.

ABSTRACT: Autophagy is a phylogenetically conserved mechanism that controls the degradation of subcellular constituents, including misfolded proteins, and damaged organelles. The progression of many neurodegenerative diseases is thought to be driven by the aggregation of misfolded proteins; therefore, autophagic activity is thought to affect disease severity to some extent. In some neurodegenerative diseases, the suppression of autophagic activity accelerates disease progression. Given that the induction of autophagy can potentially mitigate disease severity, various autophagy-inducing compounds have been developed and their efficacy has been evaluated in several rodent models of neurodegenerative diseases.

19 Review Peripheral and central autonomic nervous system: does the sympathetic or parasympathetic nervous system bear the brunt of the pathology during the course of sporadic PD? 2018

Orimo, Satoshi / Ghebremedhin, Estifanos / Gelpi, Ellen. ·Department of Neurology, Kanto Central Hospital, 6-25-1 Kami-Yoga, Setagaya-ku, Tokyo, 158-8531, Japan. orimo@kanto-ctr-hsp.com. · Institute of Clinical Neuroanatomy, J. W. Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany. · Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Barcelona, Spain. · Institute of Neurology, Medical University of Vienna, Vienna, Austria. ·Cell Tissue Res · Pubmed #29869180.

ABSTRACT: It is a well-established fact that the sympathetic, parasympathetic and enteric nervous systems are affected at early stages in Parkinson's disease (PD). However, it is not yet clarified whether the earliest pathological events preferentially occur in any of these three divisions of the autonomic nervous system (ANS). Significant involvement of the peripheral autonomic nervous system of the heart and gastrointestinal tract has been documented in PD. Accumulating evidence suggests that the PD pathology spreads centripetally from the peripheral to central nervous system through autonomic nerve fibers, implicating the ANS as a major culprit in PD pathogenesis and a potential target for therapy. This study begins with a brief overview of the structures of the central and peripheral autonomic nervous system and then outlines the major clinicopathological manifestations of cardiovascular and gastrointestinal disturbances in PD.

20 Review Getting a good night sleep? The importance of recognizing and treating nocturnal hypokinesia in Parkinson's disease. 2018

Bhidayasiri, Roongroj / Trenkwalder, Claudia. ·Chulalongkorn Center of Excellence on Parkinson Disease & Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand; Department of Rehabilitation Medicine, Juntendo University, Tokyo, Japan. Electronic address: rbh@chulapd.org. · Department of Neurosurgery, University Medical Center Gottingen, Paracelsus Elena Hospital, Kassel, Germany. ·Parkinsonism Relat Disord · Pubmed #29336905.

ABSTRACT: When Parkinson's disease (PD) patients are asked about the quality of their sleep, their answers are dominated by difficulties associated with impaired mobility in bed, medically referred to as nocturnal hypokinesia. Nocturnal hypokinesia is symptomatic from the mid-stage of the disease, affecting up to 70% of PD patients, and contributes to poor sleep quality, and increased carer burden. Here we explore four areas of nocturnal hypokinesia that are relevant to clinical practice, namely: manifestations and definition; clinical assessment and objective monitoring; etiologies and contributing factors; and evidence-based therapeutic approaches. In addition, we provide an operational definition of what constitutes nocturnal hypokinesia and outline different methods of assessment, ranging from clinical interviews and rating scales to objective night-time monitoring with inertial sensors. Optimal management of nocturnal hypokinesia in PD begins with recognizing its manifestation by inquiring about cardinal symptoms and contributing factors from, not only patients, but also carers, followed by formal assessment, and the application of individualized evidence-based treatment. Night-time dopaminergic treatment is the primary therapy; however, careful clinical judgment is required to balance the benefits with the potential adverse events related to nocturnal dopaminergic stimulation. Future studies are needed to explore the practicality of home-based objective assessment of nocturnal hypokinesia, new therapeutic options not limited to dopaminergic medications, and non-pharmacologic approaches, including training on compensatory strategies and bedroom adaptations.

21 Review Pathological role of lipid interaction with α-synuclein in Parkinson's disease. 2018

Suzuki, Mari / Sango, Kazunori / Wada, Keiji / Nagai, Yoshitaka. ·Department of Neurotherapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan; Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira 187-8502, Japan; Diabetic Neuropathy Project, Department of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, 156-8506, Japan. Electronic address: suzuki-mr@igakuken.or.jp. · Diabetic Neuropathy Project, Department of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, 156-8506, Japan. · Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira 187-8502, Japan. · Department of Neurotherapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan; Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira 187-8502, Japan. Electronic address: nagai@neurother.med.osaka-u.ac.jp. ·Neurochem Int · Pubmed #29305919.

ABSTRACT: Alpha-synuclein (αSyn) plays a central role in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In sporadic PD and DLB, normally harmless αSyn proteins without any mutations might gain toxic functions by unknown mechanisms. Thus, it is important to elucidate the factors promoting the toxic conversion of αSyn, towards understanding the pathogenesis of and developing disease-modifying therapies for PD and DLB. Accumulating biophysical and biochemical studies have demonstrated that αSyn interacts with lipid membrane, and the interaction influences αSyn oligomerization and aggregation. Furthermore, genetic and clinicopathological studies have revealed mutations in the glucocerebrosidase 1 (GBA1) gene, which encodes a degrading enzyme for the glycolipid glucosylceramide (GlcCer), as strong risk factors for PD and DLB, and we recently demonstrated that GlcCer promotes toxic conversion of αSyn. Moreover, pathological studies have shown the existence of αSyn pathology in lysosomal storage disorders (LSDs) patient' brain, in which glycosphingolipids (GSLs) is found to be accumulated. In this review, we focus on the lipids as a key factor for inducing wild-type (WT) αSyn toxic conversion, we summarize the knowledge about the interaction between αSyn and lipid membrane, and propose our hypothesis that aberrantly accumulated GSLs might contribute to the toxic conversion of αSyn. Identifying the trigger for toxic conversion of αSyn would open a new therapeutic road to attenuate or prevent crucial events leading to the formation of toxic αSyn.

22 Review Therapeutic activity of plant-derived alkaloid conophylline on metabolic syndrome and neurodegenerative disease models. 2018

Umezawa, Kazuo / Kojima, Itaru / Simizu, Siro / Lin, Yinzhi / Fukatsu, Hitomi / Koide, Naoki / Nakade, Yukiomi / Yoneda, Masashi. ·Department of Molecular Target Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan. umezawa@aichi-med-u.ac.jp. · Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, 371-8512, Japan. · Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, 223-8522, Japan. · Department of Molecular Target Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan. · Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan. ·Hum Cell · Pubmed #29249016.

ABSTRACT: Increasing metabolic syndromes including type-2 diabetes mellitus, obesity, and steatohepatitis are serious problems in most countries in the world. Neurodegenerative diseases such as Alzheimer, Parkinson's, and Huntington's diseases are increasing in many countries. However, therapy for these diseases is not sufficient yet. Thus, effective chemotherapy for these diseases is being expected. Conophylline is an alkaloid isolated from the leaves of Ervatamia microphylla and related plants. It was found to induce beta-cell differentiation in the precursor pancreatic cells. Oral administration of this compound ameliorated type-2 diabetes mellitus model in mice and rats. Later, fibrosis of the pancreatic islets was found to be greatly reduced by conophylline in the pancreatic islets. It also inhibited chemically induced liver cirrhosis. Further study indicated that conophylline inhibited non-alcoholic steatohepatitis in the model mice. On the one hand, loss of autophagy often causes protein aggregation to give neural cell death. Conophylline was found to activate autophagy in cultured neural cells. Activation of autophagy ameliorated cellular models of Parkinson's and Huntington's diseases. Thus, conophylline is likely to be useful for the development of chemotherapy for metabolic and neurodegenerative diseases.

23 Review Urological dysfunction in synucleinopathies: epidemiology, pathophysiology and management. 2018

Sakakibara, Ryuji / Tateno, Fuyuki / Yamamoto, Tatsuya / Uchiyama, Tomoyuki / Yamanishi, Tomonori. ·Neurology, Internal Medicine, Sakura Medical Center, Toho University, 564-1 Shimoshizu, Sakura, 285-8741, Japan. sakakibara@sakura.med.toho-u.ac.jp. · Neurology, Internal Medicine, Sakura Medical Center, Toho University, 564-1 Shimoshizu, Sakura, 285-8741, Japan. · Neurology, Chiba University, Chiba, Japan. · Continence Center, Dokkyo Medical College, Mibu, Japan. ·Clin Auton Res · Pubmed #29124503.

ABSTRACT: OBJECTIVE: Parkinson's disease (PD) and multiple system atrophy (MSA) are major neurogenerative diseases characterized pathologically by abnormal alpha-synuclein aggregation. PD and MSA are clinically characterized by motor disorder and bladder dysfunction (mainly urinary urgency and frequency, also called overactive bladder). However, few literatures are available concerning bladder dysfunction in PD or MSA. METHOD: A systematic review. RESULTS: The bladder dysfunction in MSA is more severe than that in PD for large post-void residual or urinary retention. These bladder dysfunctions presumably reflect the different nervous system pathologies. Overactive bladder in PD reflects lesions in the brain, e.g., in the prefrontal-nigrostriatal D1 dopaminergic bladder-inhibitory pathway. Overactive bladder in MSA reflects lesions similar to PD and the cerebellum (bladder-inhibitory), and the urinary retention in MSA presumably reflects lesions in the pontine micturition center and the sacral intermediolateral nucleus of the spinal cord (bladder-facilitatory). Bladder dysfunction not only impairs an individual's quality of life, it can also cause emergency hospitalizations due to acute retention and early institutionalization. Anticholinergics are the first-line treatment for bladder dysfunction in PD and MSA patients, but care should be taken for the management of bladder dysfunction-particularly in MSA patients due to the high prevalence of difficult emptying, which needs clean, intermittent catheterization. CONCLUSIONS: This review summarizes the epidemiology, pathophysiology, and management of bladder dysfunction in individuals with PD or MSA.

24 Review Does Parkinson's disease start in the gut? 2018

Lionnet, Arthur / Leclair-Visonneau, Laurène / Neunlist, Michel / Murayama, Shigeo / Takao, Masaki / Adler, Charles H / Derkinderen, Pascal / Beach, Thomas G. ·Department of Neurology, CHU Nantes, 44093, Nantes, France. · Inserm, U1235, 1, rue Gaston Veil, 44035, Nantes Cedex 1, France. · Nantes University, 44035, Nantes, France. · Department of Clinical Neurophysiology, CHU Nantes, 44093, Nantes, France. · Brain Bank for Aging Research, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan. · Department of Neurology, Saitama International Medical Center, Saitama Medical University, Yamane, Hidaka, Saitama, 350-1298, Japan. · Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA. · Department of Neurology, CHU Nantes, 44093, Nantes, France. derkinderenp@yahoo.fr. · Inserm, U1235, 1, rue Gaston Veil, 44035, Nantes Cedex 1, France. derkinderenp@yahoo.fr. · Nantes University, 44035, Nantes, France. derkinderenp@yahoo.fr. · Banner Sun Health Research Institute, Sun City, AZ, 85351, USA. ·Acta Neuropathol · Pubmed #29039141.

ABSTRACT: Parkinson's disease (PD) is pathologically characterized by the presence of intraneuronal inclusions, termed Lewy bodies and Lewy neurites, whose main component is alpha-synuclein. Based on the topographic distribution of Lewy bodies and neurites established after autopsy from PD patients, Braak and coworkers hypothesized that PD pathology may start in the gastrointestinal tract then spread through the vagus nerve to the brain. This hypothesis has been reinforced by the discovery that alpha-synuclein may be capable of spreading transcellularly, thereby providing a mechanistic basis for Braak's hypothesis. This 'gut to brain' scenario has ignited heated debates within the movement disorders community and prompted a large number of studies in both humans and animals. Here, we review the arguments for and against the gut as the origin of PD. We conclude that the human autopsy evidence does not support the hypothesis and that it is too early to draw any definitive conclusions. We discuss how this issue might be further addressed in future research.

25 Review [Voxel-Based Morphometry and Social Cognitive Function in Parkinson's Disease]. 2017

Kobayakawa, Mutsutaka. ·Department of Informatics, Faculty of Informatics, Tokyo University of Information Sciences. ·Brain Nerve · Pubmed #29172197.

ABSTRACT: In recent years, voxel-based morphometry (VBM) has been increasingly used to investigate local brain structures in Parkinson's disease (PD). Compared to healthy participants, PD patients tend to show reduced brain volume in limbic and paralimbic areas in early disease stages, while the neocortical areas, such as the temporal and frontal cortices, are affected in advanced patients. Moreover, there are many studies showing correlation between cognitive performance and local brain volume. In the last decade, emotional and social cognitive function, such as facial emotion recognition, emotional decision-making, and theory of mind, have been the target of VBM analysis in PD. These studies facilitate understanding of the nature of communication and behavioral disorders that some PD patients display. However, there are discrepancies in VBM results between studies. Future studies need to employ larger sample sizes and combined analysis of brain perfusion or network connectivity in order to confirm brain structural changes and their effects on social cognitive function in PD patients.

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