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
Citations
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Identification of a Novel LRRK2 Mutation Linked to Autosomal Dominant Parkinsonism: Evidence of a Common Founder across European Populations
Jennifer M. Kachergus,Ignacio F. Mata,Mary M. Hulihan,Julie P. Taylor,Sarah Lincoln,Jan O. Aasly,J. Mark Gibson,Owen A. Ross,Timothy Lynch,Timothy Lynch,Joseph Wiley,Joseph Wiley,Haydeh Payami,John G. Nutt,Demetrius M. Maraganore,Krzysztof Czyzewski,Maria Styczyńska,Zbigniew K. Wszolek,Matthew J. Farrer,Mathias Toft +19 more
TL;DR: It is demonstrated that LRRK2 G2019S accounts for parkinsonism in several families within Europe and North America, highlighting the fact that a proportion of clinically typical, late-onset PD cases have a genetic basis.
Journal ArticleDOI
Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease
Lena F. Burbulla,Lena F. Burbulla,Pingping Song,Joseph R. Mazzulli,Joseph R. Mazzulli,Enrico Zampese,Yvette C. Wong,Sohee Jeon,David Santos,Judith Blanz,Carolin D. Obermaier,Carolin D. Obermaier,Chelsee Strojny,Jeffrey N. Savas,Evangelos Kiskinis,Xiaoxi Zhuang,Rejko Krüger,Rejko Krüger,Rejko Krüger,D. James Surmeier,Dimitri Krainc,Dimitri Krainc +21 more
TL;DR: Dopaminergic neurons derived from patients with idiopathic and familial PD are studied to identify a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction, and α-synuclein accumulation.
Journal ArticleDOI
DJ-1, a novel regulator of the tumor suppressor PTEN.
Raymond H. Kim,Malte Peters,Yingju Jang,Yingju Jang,Wei Shi,Melania Pintilie,Graham C. Fletcher,Carmela DeLuca,Jennifer Liepa,Lily Zhou,Bryan E. Snow,Richard Binari,Armen S. Manoukian,Mark R. Bray,Fei-Fei Liu,Ming-Sound Tsao,Tak W. Mak,Tak W. Mak +17 more
TL;DR: DJ-1 expression was increased compared to paired nonneoplastic lung tissue, and correlated positively with relapse incidence, and is thus a key negative regulator of PTEN that may be a useful prognostic marker for cancer.
Journal ArticleDOI
High-Resolution Whole-Genome Association Study of Parkinson Disease
Demetrius M. Maraganore,Mariza de Andrade,Timothy G. Lesnick,Kari J. Strain,Matthew J. Farrer,Walter A. Rocca,P. V. Krishna Pant,Kelly A. Frazer,David Cox,Dennis G. Ballinger +9 more
TL;DR: Independent replication across populations will clarify the role of the genomic loci tagged by these SNPs in conferring PD susceptibility and test a priori biological and genetic hypotheses regarding susceptibility to PD.
Journal ArticleDOI
Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences
TL;DR: The role of mitochondria in the etiopathogenesis of Parkinson's disease has been investigated in this paper, based on the observation that mitochondrial toxins can cause parkinsonism in humans and animal models.
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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