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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Journal ArticleDOI
Monogenic Parkinson's disease and parkinsonism: Clinical phenotypes and frequencies of known mutations.
TL;DR: Clinical features of diseases caused by mutations in SNCA cause cognitive or psychiatric symptoms, parkinsonism, dysautonomia and myoclonus with widespread alpha-synuclein pathology in the central and peripheral nervous system.
Journal ArticleDOI
CHIP: a quality-control E3 ligase collaborating with molecular chaperones.
TL;DR: CHIP is an ideal molecule acting as a protein quality-control ubiquitin ligase that selectively leads abnormal proteins recognized by molecular chaperones to degradation by the proteasome, accumulating evidence from in vitro studies indicates.
Journal ArticleDOI
Multiple candidate gene analysis identifies α-synuclein as a susceptibility gene for sporadic Parkinson's disease
Ikuko Mizuta,Wataru Satake,Yuko Nakabayashi,Chiyomi Ito,Satoko Suzuki,Yoshio Momose,Yoshitaka Nagai,Akira Oka,Hidetoshi Inoko,Jiro Fukae,Yuko Saito,Motoji Sawabe,Shigeo Murayama,Mitsutoshi Yamamoto,Nobutaka Hattori,Miho Murata,Tatsushi Toda +16 more
TL;DR: Findings establish SNCA as a definite susceptibility gene for sporadic PD, a major component of Lewy bodies, the pathological hallmark of PD.
Journal ArticleDOI
The PARK8 Locus in Autosomal Dominant Parkinsonism: Confirmation of Linkage and Further Delineation of the Disease-Containing Interval
Alexander Zimprich,Bertram Müller-Myhsok,Matthew J. Farrer,Petra Leitner,Manu Sharma,Mary M. Hulihan,Paul J. Lockhart,Audrey Strongosky,Jennifer M. Kachergus,Donald B. Calne,Jon Stoessl,Ryan J. Uitti,Ronald F. Pfeiffer,Claudia Trenkwalder,Nikolaus Homann,Erwin Ott,Karoline Wenzel,Friedrich Asmus,John Hardy,Zbigniew K. Wszolek,Thomas Gasser +20 more
TL;DR: The data provide evidence that the PARK8 locus is responsible for the disease in a subset of families of white ancestry with autosomal dominant parkinsonism, suggesting that it could be a more common locus.
Journal ArticleDOI
The Mitochondrial Basis of Aging and Age-Related Disorders.
TL;DR: The current understanding on how mitochondrial functional decline contributes to aging is reviewed, including the role of somatic mitochondrial DNA mutations, reactive oxygen species (ROS), mitochondrial dynamics and quality control pathways, and the emerging evidence on how dysregulated mitochondrial dynamics, mitochondrial biogenesis and turnover mechanisms contribute to the pathogenesis of age-related disorders.
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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