Journal ArticleDOI
Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism
Vincenzo Bonifati,Vincenzo Bonifati,Patrizia Rizzu,Marijke J. van Baren,Onno Schaap,Guido J. Breedveld,Elmar Krieger,Marieke C. J. Dekker,Ferdinando Squitieri,Pablo Ibanez,Marijke Joosse,Jeroen W.F. van Dongen,Nicola Vanacore,Nicola Vanacore,John C. van Swieten,Alexis Brice,Giuseppe Meco,Cornelia M. van Duijn,Ben A. Oostra,Peter Heutink +19 more
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TLDR
It is shown that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism, and these findings indicate that loss ofDJ-1 function leads to neurodegeneration.Abstract:
The DJ-1 gene encodes a ubiquitous, highly conserved protein. Here, we show that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism. The function of the DJ-1 protein remains unknown, but evidence suggests its involvement in the oxidative stress response. Our findings indicate that loss of DJ-1 function leads to neurodegeneration. Elucidating the physiological role of DJ-1 protein may promote understanding of the mechanisms of brain neuronal maintenance and pathogenesis of Parkinson's disease.read more
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Journal ArticleDOI
Intersecting pathways to neurodegeneration in Parkinson's disease: Effects of the pesticide rotenone on DJ-1, α-synuclein, and the ubiquitin–proteasome system
Ranjita Betarbet,Rosa M. Canet-Avilés,Todd B. Sherer,Pier G. Mastroberardino,Chris McLendon,Jin Ho Kim,Serena Lund,Hye-Mee Na,Georgia Taylor,Neil F. Bence,Ron R. Kopito,Byoung Boo Seo,Takao Yagi,Akemi Yagi,Gary R. Klinefelter,Mark R. Cookson,J. Timothy Greenamyre +16 more
TL;DR: Chronic exposure to a pesticide and mitochondrial toxin brings into play three systems, DJ-1, alpha-synuclein, and the ubiquitin-proteasome system, and implies that mitochondrial dysfunction and oxidative stress link environmental and genetic forms of the disease.
Journal ArticleDOI
Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1.
Guido Krebiehl,Sabine Ruckerbauer,Lena F. Burbulla,Nicole Kieper,Brigitte Maurer,Jens Waak,Hartwig Wolburg,Zemfira Gizatullina,Frank N. Gellerich,Dirk Woitalla,Olaf Riess,Philipp J. Kahle,Tassula Proikas-Cezanne,Rejko Krüger +13 more
TL;DR: It is shown that loss of DJ-1 leads to impaired autophagy and accumulation of dysfunctional mitochondria that under physiological conditions would be compensated via lysosomal clearance, providing evidence for a critical role ofDJ-1 in mitochondrial homeostasis in Parkinson's disease.
Journal ArticleDOI
Gene expression profiling of parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes
Edna Grünblatt,Silvia Mandel,J. Jacob-Hirsch,Sharon Zeligson,N. Amariglo,Gideon Rechavi,J. Li,Rivka Ravid,Wolfgang Roggendorf,P. Riederer,Moussa B.H. Youdim +10 more
TL;DR: One major finding is the particular decreased expression of SKP1A, a member of the SCF (E3) ligase complex specifically in the substantia nigra (SN) of sporadic parkinsonian patients, which may lead to a wide impairment in the function of an entire repertoire of proteins subjected to regulatory ubiquitination.
Journal ArticleDOI
The genetics of Parkinson disease.
TL;DR: This work provides a comprehensive and critical overview of the current clinical, neuropathological, and genetic understanding of genetic forms of Parkinson disease and discusses advances in screening for genetic PD-related risk factors.
Journal ArticleDOI
The Role of Environmental Exposures in Neurodegeneration and Neurodegenerative Diseases
TL;DR: The role of neurotoxicant exposures in neurodegenerative disease has long been suspected, with much effort devoted to identifying causative agents, but causative factors for a significant number of cases have yet to be identified.
References
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