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
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TLDR
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’.Abstract:
Parkinson's disease is a common neurodegenerative disease with complex clinical features1. Autosomal recessive juvenile parkinsonism (AR-JP)2,3 maps to the long arm of chromosome 6 (6q25.2-q27) and is linked strongly to the markers D6S305 and D6S253 (ref. 4); the former is deleted in one Japanese AR-JP patient5. By positional cloning within this microdeletion, we have now isolated a complementary DNA clone of 2,960 base pairs with a 1,395-base-pair open reading frame, encoding a protein of 465 amino acids with moderate similarity to ubiquitin at the amino terminus and a RING-finger motif at the carboxy terminus. The gene spans more than 500 kilobases and has 12 exons, five of which (exons 3–7) are deleted in the patient. Four other AR-JP patients from three unrelated families have a deletion affecting exon 4 alone. A 4.5-kilobase transcript that is expressed in many human tissues but is abundant in the brain, including the substantia nigra, is shorter in brain tissue from one of the groups of exon-4-deleted patients. Mutations in the newly identified gene appear to be responsible for the pathogenesis of AR-JP, and we have therefore named the protein product ‘Parkin’.read more
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Bioenergetics of neurons inhibit the translocation response of Parkin following rapid mitochondrial depolarization
Victor S. Van Laar,Beth Arnold,Steven J. Cassady,Charleen T. Chu,Edward A. Burton,Sarah B. Berman +5 more
TL;DR: In neurons, unlike other cells, mitochondrial depolarization by carbonyl cyanide m-chlorophenyl hydrazone did not induce Parkin translocation to mitochondria or mitophagy, and this data suggest that changes in ATP levels are not the sole determinant of the different responses between neurons and other cell types, and imply that additional mechanisms regulateMitophagy in neurons.
Journal ArticleDOI
Protein degradation pathways in Parkinson's disease: curse or blessing.
Darius Ebrahimi-Fakhari,Darius Ebrahimi-Fakhari,Lara Wahlster,Lara Wahlster,Pamela J. McLean,Pamela J. McLean +5 more
TL;DR: The role of protein degradation pathways in Parkinson’s disease is reviewed and elaborate on the different contributions of the UPS and the ALP to the clearance of altered proteins, as well as examining the interplay between different degradation pathways.
Journal ArticleDOI
Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease.
Linda B. Moran,Dawn C. Duke,Manuel Deprez,David T. Dexter,Ronald K. B. Pearce,Manuel B. Graeber +5 more
TL;DR: This work used brain tissue from clinically well-documented and neuropathologically confirmed cases of sporadic Parkinson’s disease to establish the transcriptomic expression profile of the medial and lateral substantia nigra and several new candidate genes which map to PARK loci are reported.
Journal ArticleDOI
A Neo-Substrate that Amplifies Catalytic Activity of Parkinson’s-Disease-Related Kinase PINK1
Nicholas T. Hertz,Amandine Berthet,Martin L. Sos,Kurt S. Thorn,Al Burlingame,Ken Nakamura,Kevan M. Shokat +6 more
TL;DR: Application of the KTP precursor kinetin to cells results in biologically significant increases in PINK1 activity, manifest as higher levels of Parkin recruitment to depolarized mitochondria, reduced mitochondrial motility in axons, and lower levels of apoptosis.
Journal ArticleDOI
SOD2 in mitochondrial dysfunction and neurodegeneration.
James M. Flynn,Simon Melov +1 more
TL;DR: SOD2's potential involvement in the progression of neurodegenerative diseases such as stroke and Alzheimer and Parkinson diseases, as well as its potential role in "normal" age-related cognitive decline are reviewed.
References
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Book
Molecular Cloning: A Laboratory Manual
TL;DR: Molecular Cloning has served as the foundation of technical expertise in labs worldwide for 30 years as mentioned in this paper and has been so popular, or so influential, that no other manual has been more widely used and influential.
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
Alpha-synuclein in Lewy bodies.
Maria Grazia Spillantini,Marie L. Schmidt,Virginia M.-Y. Lee,John Q. Trojanowski,Ross Jakes,Michel Goedert +5 more
TL;DR: Strong staining of Lewy bodies from idiopathic Parkinson's disease with antibodies for α-synuclein, a presynaptic protein of unknown function which is mutated in some familial cases of the disease, indicates that the LewY bodies from these two diseases may have identical compositions.
Journal ArticleDOI
Mitochondrial complex I deficiency in Parkinson's disease.
TL;DR: Results indicated a specific defect of Complex I activity in the substantia nigra of patients with Parkinson's disease, which adds further support to the proposition that Parkinson’s disease may be due to an environmental toxin with action(s) similar to those of MPTP.
Journal ArticleDOI
The ubiquitin-proteasome proteolytic pathway
TL;DR: Two studies clearly demonstrate that the ubiquitin-proteasome system is involved not only in complete destruction of its protein substrates, but also in limited proteolysis and posttranslational processing in which biologically active peptides or fragments are generated.
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