Journal ArticleDOI
Genetics of Parkinson disease: paradigm shifts and future prospects.
TLDR
Genetic insights provide the rationale for new strategies for prevention or therapy, and have led to animal models of disease in which these strategies can be tested.Abstract:
Parkinson disease is a complex, multifactorial neurodegenerative disease. Although a heritable basis was originally thought unlikely, recent studies have implicated several genes in its pathogenesis, and molecular findings now allow accurate diagnosis and challenge past criteria for defining Parkinson disease. Most importantly, genetic insights provide the rationale for new strategies for prevention or therapy, and have led to animal models of disease in which these strategies can be tested. Neuroprotective therapies can now be designed to slow or halt disease progression in affected subjects and asymptomatic carriers.read more
Citations
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Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease
Wataru Satake,Yuko Nakabayashi,Yuko Nakabayashi,Ikuko Mizuta,Ikuko Mizuta,Yushi Hirota,Yushi Hirota,Chiyomi Ito,Chiyomi Ito,Michiaki Kubo,Takahisa Kawaguchi,Tatsuhiko Tsunoda,Masahiko Watanabe,Atsushi Takeda,Hiroyuki Tomiyama,Kenji Nakashima,Kazuko Hasegawa,Fumiya Obata,Takeo Yoshikawa,Hideshi Kawakami,Saburo Sakoda,Mitsutoshi Yamamoto,Nobutaka Hattori,Miho Murata,Yusuke Nakamura,Tatsushi Toda,Tatsushi Toda +26 more
TL;DR: The results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.
Journal ArticleDOI
Cellular Stress Responses: Cell Survival and Cell Death
TL;DR: The implications of cellular stress responses to human physiology and diseases are manifold and will be discussed in this review in the context of some major world health issues such as diabetes, Parkinson's disease, myocardial infarction, and cancer.
Journal ArticleDOI
A Nurr1/CoREST Pathway in Microglia and Astrocytes Protects Dopaminergic Neurons from Inflammation-Induced Death
Kaoru Saijo,Beate Winner,Christian T. Carson,Jana G. Collier,Leah Boyer,Leah Boyer,Michael G. Rosenfeld,Fred H. Gage,Christopher K. Glass +8 more
TL;DR: It is demonstrated that Nurr1 unexpectedly functions to inhibit expression of pro-inflammatory neurotoxic mediators in both microglia and astrocytes, and protects against loss of dopaminergic neurons in Parkinson's disease in part by limiting the production of neurot toxic mediators by microglIA and ast rocytes.
Journal ArticleDOI
VPS35 Mutations in Parkinson Disease
Carles Vilariño-Güell,Christian Wider,Owen A. Ross,Justus C. Dachsel,Jennifer M. Kachergus,Sarah Lincoln,Alexandra I. Soto-Ortolaza,Stephanie A. Cobb,Greggory J. Wilhoite,Justin A. Bacon,Behrouz Bahareh Behrouz,Heather L. Melrose,Emna Hentati,Andreas Puschmann,Andreas Puschmann,Daniel M. Evans,Elizabeth Conibear,Wyeth W. Wasserman,Jan O. Aasly,Pierre R. Burkhard,Ruth Djaldetti,Joseph Ghika,Fayçal Hentati,Anna Krygowska-Wajs,Timothy Lynch,Timothy Lynch,Eldad Melamed,Alex Rajput,Ali H. Rajput,Alessandra Solida,Ruey-Meei Wu,Ryan J. Uitti,Zbigniew K. Wszolek,François Vingerhoets,Matthew J. Farrer,Matthew J. Farrer +35 more
TL;DR: This study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.
Journal ArticleDOI
Missing pieces in the Parkinson's disease puzzle.
Jose A. Obeso,Maria C. Rodriguez-Oroz,Christopher G. Goetz,Concepcion Marin,Concepcion Marin,Jeffrey H. Kordower,Manuel Rodriguez,Manuel Rodriguez,Etienne C. Hirsch,Matthew J. Farrer,Anthony H.V. Schapira,Glenda M. Halliday +11 more
TL;DR: A series of critical issues that researchers need to address to stand a better chance of solving the different challenges posed by Parkinson's disease are discussed.
References
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Journal ArticleDOI
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
TL;DR: A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Journal ArticleDOI
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Tohru Kitada,Shuichi Asakawa,Nobutaka Hattori,Hiroto Matsumine,Yasuhiro Yamamura,Shinsei Minoshima,Masayuki Yokochi,Yoshikuni Mizuno,Nobuyoshi Shimizu +8 more
TL;DR: Mutations in the newly identified gene appear to be responsible for the pathogenesis of Autosomal recessive juvenile parkinsonism, and the protein product is named ‘Parkin’.
Journal ArticleDOI
Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis
TL;DR: It is proposed that this chemical selectively damages cells in the substantia nigra in patients who developed marked parkinsonism after using an illicit drug intravenously.
Journal ArticleDOI
α-Synuclein Locus Triplication Causes Parkinson's Disease
Andrew B. Singleton,Matthew J. Farrer,Joshua C. Johnson,Amanda Singleton,Stephen Hague,Jennifer M. Kachergus,Mary M. Hulihan,Terhi Peuralinna,Amalia Dutra,Robert L. Nussbaum,Sarah Lincoln,Anthony Crawley,Melissa Hanson,Demetrius M. Maraganore,Charles H. Adler,Mark R. Cookson,Manfred D. Muenter,Melisa J. Baptista,David Miller,J. Blancato,John Hardy,Katrina Gwinn-Hardy +21 more
TL;DR: In this article, the α-synuclein was identified as the major component of Lewy bodies, the pathological hallmark of Parkinson's disease, and of glial cell cytoplasmic inclusions.
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