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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PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons.
Alison Wood-Kaczmar,Sonia Gandhi,Zhi Yao,Andrey Y. Abramov,Erik Miljan,Gregory Keen,Lee Stanyer,Iain P. Hargreaves,Kristina Klupsch,Emma Deas,Julian Downward,Louise Mansfield,Parmjit S. Jat,Joanne Taylor,Simon J.R. Heales,Michael R. Duchen,David S. Latchman,Sarah J. Tabrizi,Nicholas W. Wood +18 more
TL;DR: It is reported that PINK1 plays a neuroprotective role in the mitochondria of mammalian neurons, especially against stress such as staurosporine, and evidence that cellular compensatory mechanisms such as mitochondrial biogenesis and upregulation of lysosomal degradation pathways occur in Pink1 deficiency.
Journal ArticleDOI
PINK1 protein in normal human brain and Parkinson's disease
Sonia Gandhi,Miratul M. K. Muqit,Lee Stanyer,Daniel G. Healy,Patrick M. Abou-Sleiman,Iain P. Hargreaves,Simon J.R. Heales,M Ganguly,L Parsons,A J Lees,David S. Latchman,Janice L. Holton,Nicholas W. Wood,Tamas Revesz +13 more
TL;DR: In vivo morphological and biochemical evidence is provided for the first time to support a mitochondrial localization of PINK1 and underpin the significance of mitochondrial dysfunction in the pathogenesis of nigral cell degeneration in Parkinson's disease.
Journal ArticleDOI
ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease.
A. Di Fonzo,Hsin Fen Chien,M. Socal,S. Giraudo,Cristina Tassorelli,G. Iliceto,Giovanni Fabbrini,Roberto Marconi,E. Fincati,Giovanni Abbruzzese,P. Marini,Ferdinando Squitieri,Martin W.I.M. Horstink,Pasquale Montagna,A. Dalla Libera,Fabrizio Stocchi,Stefano Goldwurm,Joaquim J. Ferreira,Giuseppe Meco,Emilia Martignoni,Leonardo Lopiano,Laura Bannach Jardim,Ben A. Oostra,Egberto Reis Barbosa,Vincenzo Bonifati +24 more
TL;DR: It is confirmed that ATP13A2 homozygous mutations are associated with human parkinsonism, and the associated genotypic and clinical spectrum is expanded, by describing a homozygOUS missense mutation in this gene in a patient with a phenotype milder than that initially associated with ATP 13A2 mutations (Kufor-Rakeb syndrome).
Journal ArticleDOI
The role of parkin in familial and sporadic Parkinson's disease.
Ted M. Dawson,Valina L. Dawson +1 more
TL;DR: Parkin is an ubiquitin E3 ligase that monoubiquitinates and polyubiquitate proteins to regulate a variety of cellular processes and its role in the pathogenesis of PD is reviewed.
Journal ArticleDOI
Paraquat exposure as an etiological factor of Parkinson's disease.
Ricardo Jorge Dinis-Oliveira,Fernando Remião,Helena Carmo,José Alberto Duarte,A. Sánchez Navarro,Maria de Lourdes Bastos,Félix Carvalho +6 more
TL;DR: PQ-induced lipid peroxidation and consequent cell death of dopaminergic neurons can be responsible for the onset of the Parkinsonian syndrome, thus indicating that this herbicide may induce PD or influence its natural course.
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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