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
Mitochondria in the aetiology and pathogenesis of Parkinson's disease.
TL;DR: Insights into the aetiology and pathogenesis of PD provide hope that drugs or cocktails of drugs that might successfully intervene in the pathogenesis and slow the progression of the disease can be derived from the study of the converging rather than diverging pathways to cell dysfunction and death.
Journal ArticleDOI
A Mutation in VPS35, Encoding a Subunit of the Retromer Complex, Causes Late-Onset Parkinson Disease
Alexander Zimprich,Anna Benet-Pagès,Walter Struhal,Elisabeth Graf,Sebastian H. Eck,Marc N. Offman,Dietrich Haubenberger,Sabine Spielberger,Eva C. Schulte,Peter Lichtner,Shaila C. Rossle,Norman Klopp,Elisabeth Wolf,Klaus Seppi,Walter Pirker,Stefan Presslauer,Brit Mollenhauer,Regina Katzenschlager,Thomas Foki,Christoph Hotzy,Eva M. Reinthaler,Ashot S. Harutyunyan,Robert Kralovics,Annette Peters,Fritz Zimprich,Thomas Brücke,Werner Poewe,Eduard Auff,Claudia Trenkwalder,Burkhard Rost,Gerhard Ransmayr,Juliane Winkelmann,Thomas Meitinger,Tim M. Strom +33 more
TL;DR: An Austrian family with 16 affected individuals by exome sequencing found a missense mutation, c.1858G>A (p.Asp620Asn), in the VPS35 gene in all seven affected family members who are alive, and found the same variant cosegregating with the disease in an autosomal-dominant mode with high but incomplete penetrance.
Journal ArticleDOI
Dopamine-mediated regulation of corticostriatal synaptic plasticity
TL;DR: A model in which the spontaneous membrane oscillations of neurons projecting from the striatum, in addition to the pattern of release of endogenous dopamine, bias the synapse towards preferential induction of LTP or LTD is proposed.
Journal ArticleDOI
Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1
Jaime N. Guzman,Javier Sanchez-Padilla,David L. Wokosin,Jyothisri Kondapalli,Ema Ilijic,Paul T. Schumacker,D. James Surmeier +6 more
TL;DR: It is shown, using transgenic mice that expressed a redox-sensitive variant of green fluorescent protein targeted to the mitochondrial matrix, that the engagement of plasma membrane L-type calcium channels during normal autonomous pacemaking created an oxidant stress that was specific to vulnerable SNc dopaminergic neurons.
Journal ArticleDOI
Genetic animal models of Parkinson's disease.
TL;DR: The animal models for these genetic causes of PD, including mutations in LRRK2 and alpha-synuclein and mutations in parkin, DJ-1, and PINK1, are discussed, their limitations, and value.
References
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Daisuke Nagakubo,Takahiro Taira,Hirotake Kitaura,Masako Ikeda,Katsuyuki Tamai,Sanae M.M. Iguchi-Ariga,Hiroyoshi Ariga +6 more
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