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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Journal ArticleDOI
The genetics and neuropathology of Parkinson's disease.
TL;DR: The genetic, clinical and pathological findings of autosomal dominant disease linked to mutations in SNCA, LRRK2, ATXN2,ATXN3, MAPT, GCH1, DCTN1 and VPS35 are summarized.
Journal ArticleDOI
Autophagy in acute kidney injury.
Gur P. Kaushal,Sudhir V. Shah +1 more
TL;DR: In models of AKI, autophagy deletion in proximal tubules worsened tubular injury and renal function, highlighting thatAutophagy is renoprotective in models ofAKI and pose potentially unique targets for therapeutic interventions in AKI.
Journal ArticleDOI
Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation.
Jose A. Rodriguez-Navarro,Laura Zúñiga Rodríguez,María José Casarejos,Rosa M. Solano,Ana Gómez,Juan Perucho,Ana Maria Cuervo,Justo García de Yébenes,Maria Angeles Mena +8 more
TL;DR: This study develops and characterized a mouse model of tauopathy with parkinsonism, overexpressing human mutated tau protein with deletion of parkin, and opens the way for clinical studies of the effects of trehalose in human tauopathies.
Journal ArticleDOI
Oxidative damage to macromolecules in human Parkinson disease and the rotenone model.
TL;DR: The recent evidence for oxidative damage to nucleic acids, lipids, and proteins in both the brain and the peripheral tissues in human PD and in the rotenone model is reviewed.
PatentDOI
A susceptibility gene for late-onset idiopathic parkinson's disease
TL;DR: In this paper, Park8 therapeutic agents, including the PARK8 nucleic acids, Park8 polypeptides, or agents that alter the activity of an PARK8polypeptide, as well as pharmaceutical compositions comprising the PARK 8 therapeutic agents are disclosed.
References
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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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