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
Citations
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Neuroprotective Effects Of Curcumin
TL;DR: Dietary CUR, the principal curcuminoid of turmeric, is now recognized as being responsible for most of the therapeutic effects and it has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial and antifungal as well as anticancer activities.
Journal ArticleDOI
An inhibitor of mitochondrial complex I, rotenone, inactivates proteasome by oxidative modification and induces aggregation of oxidized proteins in SH-SY5Y cells
Masayo Shamoto-Nagai,Wakako Maruyama,Yoji Kato,Ken-ichi Isobe,Masashi Tanaka,Makoto Naoi,Toshihiko Osawa +6 more
TL;DR: It is suggested that mitochondrial dysfunction, especially decreased activity of complex I, may reduce proteasome activity through oxidative modification of proteasomes itself and aggregation with other oxidized proteins, which might account for the accumulation of modified protein and, at least partially, for cell death of the dopamine neurons in Parkinson's disease.
Journal ArticleDOI
Roles of Autophagy in Oxidative Stress.
TL;DR: The basic mechanism and function of autophagy in the context of response to oxidative stress and redox signalling in pathology is attempts to provide an overview.
Journal ArticleDOI
Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease
Frank P. Marx,Carsten Holzmann,Karsten M. Strauss,Lei Li,Lei Li,Olaf Eberhardt,Ellen Gerhardt,Mark R. Cookson,Dena G. Hernandez,Matthew J. Farrer,Jennifer M. Kachergus,Simone Engelender,Christopher A. Ross,Klaus Berger,Ludger Schöls,Jörg B. Schulz,Olaf Riess,Rejko Krüger +17 more
TL;DR: The findings argue in favour of a causative role of the R621C mutation in the synphilin-1 gene in PD and suggest that the formation of intracellular inclusions may be beneficial to cells and that a mutation in synphilIn-1 that reduces this ability may sensitize neurons to cellular stress.
Journal ArticleDOI
Syndromic parkinsonism and dementia associated with OPA1 missense mutations
Valerio Carelli,Olimpia Musumeci,Leonardo Caporali,Claudia Zanna,Chiara La Morgia,Valentina Del Dotto,Anna Maria Porcelli,Michela Rugolo,Maria Lucia Valentino,Luisa Iommarini,Alessandra Maresca,Piero Barboni,Michele Carbonelli,Costantino Trombetta,Enza Maria Valente,Simone Patergnani,Carlotta Giorgi,Paolo Pinton,Giovanni Rizzo,Caterina Tonon,Raffaele Lodi,Patrizia Avoni,Rocco Liguori,Agostino Baruzzi,Antonio Toscano,Massimo Zeviani +25 more
TL;DR: 2 Italian families affected by dominant chronic progressive external ophthalmoplegia (CPEO) complicated by parkinsonism and dementia are reported.
References
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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
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