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
Sumoylation is critical for DJ-1 to repress p53 transcriptional activity
TL;DR: DJ‐1(K130R), the non‐sumoylatable mutant form of DJ‐1, shifts from nucleus to cytoplasm, fails to repress p53 transcriptional activity and loses its protective function against ultraviolet induced cell death.
Journal ArticleDOI
Silent Information Regulator 2 (Sir2) and Forkhead Box O (FOXO) Complement Mitochondrial Dysfunction and Dopaminergic Neuron Loss in Drosophila PTEN-induced Kinase 1 (PINK1) Null Mutant *
TL;DR: The strong genetic and functional interactions suggest that Sir2 and FOXO protect mitochondria and dopaminergic neuron downstream of PINK1 and independently of Parkin, supporting the idea that Sir 2, FOXO, and Pink1 protect DA neuron in a common pathway.
Journal ArticleDOI
Reactive oxygen species regulate activity-dependent neuronal plasticity in Drosophila.
Matthew C. W. Oswald,Paul S Brooks,Maarten Zwart,Amrita Mukherjee,Ryan J. H. West,Carlo N.G. Giachello,Khomgrit Morarach,Richard A. Baines,Sean T. Sweeney,Matthias Landgraf +9 more
TL;DR: This study identified the highly conserved Parkinson’s disease-linked protein DJ-1β as a redox sensor in neurons where it regulates structural plasticity, in part via modulation of the PTEN-PI3Kinase pathway.
Journal ArticleDOI
Trumping neurodegeneration: Targeting common pathways regulated by autosomal recessive Parkinson's disease genes.
TL;DR: Understanding how aberrancy in these common processes leads to neurodegeneration has provided the field with numerous targets that may be therapeutically relevant to the development of disease-modifying treatments.
Journal ArticleDOI
DJ-1/PARK7: A New Therapeutic Target for Neurodegenerative Disorders
TL;DR: DJ-1 and DJ-1-targeting molecules/compounds will be useful therapeutic targets for various neurodegenerative disorders due to their various functions such as antioxidant capacity, chaperone function and as a proteolytic pathway.
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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