Parkin-deficient Mice Exhibit Nigrostriatal Deficits but Not Loss of Dopaminergic Neurons
Matthew S. Goldberg,Sheila M. Fleming,James Palacino,Carlos Cepeda,Hoa A. Lam,Anushree Bhatnagar,Edward G. Meloni,Nanping Wu,Larry C. Ackerson,Gloria J. Klapstein,Mahadevan Gajendiran,Bryan L. Roth,Marie-Françoise Chesselet,Nigel T. Maidment,Michael Levine,Jie Shen +15 more
TLDR
A mouse model bearing a germline disruption in parkin is generated, providing the first evidence for a novel role of parkin in dopamine regulation and nigrostriatal function, and a non-essential role in the survival of nigral neurons in mice.About:
This article is published in Journal of Biological Chemistry.The article was published on 2003-10-31 and is currently open access. It has received 861 citations till now. The article focuses on the topics: Parkin & Nigrostriatal pathway.read more
Citations
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The Roles of PINK1, Parkin and Mitochondrial Fidelity in Parkinson's Disease
TL;DR: Biochemical and genetic studies reveal that the products of two genes that are mutated in autosomal recessive parkinsonism, PINK1 and Parkin, normally work together in the same pathway to govern mitochondrial quality control, bolstering previous evidence that mitochondrial damage is involved in Parkinson's disease.
Journal ArticleDOI
PINK1-dependent recruitment of Parkin to mitochondria in mitophagy
Cristofol Vives-Bauza,Chun Zhou,Yong Huang,Mei Cui,Rosa L.A. de Vries,Jiho Kim,Jessica May,Maja Aleksandra Tocilescu,Wencheng Liu,Han Seok Ko,Jordi Magrané,Darren J. Moore,Darren J. Moore,Valina L. Dawson,Regis Grailhe,Ted M. Dawson,Chenjian Li,Kim Tieu,Serge Przedborski +18 more
TL;DR: It is suggested that Parkin, together with PINK1, modulates mitochondrial trafficking, especially to the perinuclear region, a subcellular area associated with autophagy, which may alter mitochondrial turnover which, in turn, may cause the accumulation of defective mitochondria and, ultimately, neurodegeneration in Parkinson's disease.
Journal ArticleDOI
Molecular pathophysiology of parkinson's disease
TL;DR: Increasing evidence indicates that deficits in mitochondrial function, oxidative and nitrosative stress, the accumulation of aberrant or misfolded proteins, and ubiquitin-proteasome system dysfunction may represent the principal molecular pathways or events that commonly underlie the pathogenesis of sporadic and familial forms of PD.
Journal ArticleDOI
PINK1 and Parkin Target Miro for Phosphorylation and Degradation to Arrest Mitochondrial Motility
Xinnan Wang,Dominic Winter,Ghazaleh Ashrafi,Ghazaleh Ashrafi,Julia S. Schlehe,Yao Liang Wong,Dennis J. Selkoe,Sarah E. Rice,Judith A. Steen,Matthew J. LaVoie,Thomas Schwarz,Thomas Schwarz +11 more
TL;DR: It is proposed that PINK1 phosphorylation of substrates triggers the subsequent action of Parkin and the proteasome, and the PINK/Parkin pathway may quarantine damaged mitochondria prior to their clearance.
Journal ArticleDOI
The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg.
Aaron Ciechanover,Patrik Brundin +1 more
TL;DR: Recent findings indicate that the ubiquitin-proteasome system is involved in the pathogenesis of Parkinson's, Alzheimer's, Huntington's, and Prion diseases as well as amyotrophic lateral sclerosis, which raises hopes for a better understanding of the pathogenetic mechanisms involved in these diseases and for the development of novel, mechanism-based therapeutic modalities.
References
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Journal ArticleDOI
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
TL;DR: A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Journal ArticleDOI
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Tohru Kitada,Shuichi Asakawa,Nobutaka Hattori,Hiroto Matsumine,Yasuhiro Yamamura,Shinsei Minoshima,Masayuki Yokochi,Yoshikuni Mizuno,Nobuyoshi Shimizu +8 more
TL;DR: Mutations in the newly identified gene appear to be responsible for the pathogenesis of Autosomal recessive juvenile parkinsonism, and the protein product is named ‘Parkin’.
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
TL;DR: 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.
Journal ArticleDOI
The unbiased estimation of number and sizes of arbitrary particles using the disector
TL;DR: A three‐dimensional counting rule and its integral test system, the disector, for obtaining unbiased estimates of the number of arbitrary particles in a specimen is presented.
Journal ArticleDOI
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Hideki Shimura,Nobutaka Hattori,Shin-ichiro Kubo,Yoshikuni Mizuno,Shuichi Asakawa,Shinsei Minoshima,Nobuyoshi Shimizu,Kazuhiro Iwai,Tomoki Chiba,Keiji Tanaka,Toshiaki Suzuki +10 more
TL;DR: The findings indicate that accumulation of proteins that have yet to be identified causes a selective neural cell death without formation of Lewy bodies, and should enhance the exploration of the molecular mechanisms of neurodegeneration in Parkinson disease as well as in other Neurodegenerative diseases that are characterized by involvement of abnormal protein ubiquitination.
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