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
Moderate Reduction of γ-Secretase Attenuates Amyloid Burden and Limits Mechanism-Based Liabilities
Tong Li,Hongjin Wen,Cory Brayton,Fiona M. Laird,Guojun Ma,Guojun Ma,Shiwen Peng,Lisa Placanica,T-C Wu,Barbara J. Crain,Donald L. Price,Charles G. Eberhart,Philip C. Wong +12 more
TL;DR: It is demonstrated that there exists a critical γ-secretase level that reduces the risk of amyloidosis in the CNS and limits tumorigenesis in epithelia and suggested that moderate inhibition of this aspartyl protease represents an attractive anti-amyloid therapy for Alzheimer's disease.
Journal ArticleDOI
DJ-1, PINK1, and their effects on mitochondrial pathways.
TL;DR: This short review of genetic forms of parkinsonism will discuss how some of this information can be used to understand why it is that neurons become dysfunctional in PD.
Journal ArticleDOI
DJ-1 knock-down impairs astrocyte mitochondrial function.
TL;DR: It is demonstrated that DJ-1 deficiency can impair astrocyte mitochondrial physiology at multiple levels, astroCyte mitochondrial dynamics vary with sub-cellular region, and the physical presence of neurons can affect astroicyte mitochondrial behavior.
Journal ArticleDOI
Structural determinants of the C-terminal helix-kink-helix motif essential for protein stability and survival promoting activity of DJ-1.
Karin Görner,Eve Holtorf,Jens Waak,Thu-Trang Pham,Daniela Vogt-Weisenhorn,Wolfgang Wurst,Christian Haass,Philipp J. Kahle,Philipp J. Kahle +8 more
TL;DR: The G-helix and kink are critical determinants of the C-terminal helix-kink- Helix motif, which is absolutely required for stability and the regulation of survival-promoting redox signaling of the Parkinson disease-associated protein DJ-1.
Journal ArticleDOI
Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease.
Maxime W.C. Rousseaux,Paul C. Marcogliese,Dianbo Qu,Sarah Hewitt,Sarah Seang,Raymond H. Kim,Ruth S. Slack,Michael G. Schlossmacher,Michael G. Schlossmacher,Diane C. Lagace,Tak W. Mak,David S. Park,David S. Park +12 more
TL;DR: By exome sequencing, candidate modifying genes that segregate with the phenotype are identified, providing potentially critical clues into how certain genes may influence the penetrance of DJ-1–related degeneration in mice.
References
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DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras.
Daisuke Nagakubo,Takahiro Taira,Hirotake Kitaura,Masako Ikeda,Katsuyuki Tamai,Sanae M.M. Iguchi-Ariga,Hiroyoshi Ariga +6 more
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