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
A molecular explanation for the recessive nature of parkin-linked Parkinson's disease.
Donald E. Spratt,R. Julio Martinez-Torres,Yeong J. Noh,Pascal Mercier,Noah Manczyk,Kathryn R. Barber,Jacob D. Aguirre,Lynn Burchell,Andrew Purkiss,Helen Walden,Gary S. Shaw +10 more
TL;DR: It is shown that the structure of parkin RING2 is distinct from canonical RING E3 ligases and lacks key elements required for E2-conjugating enzyme recruitment, providing a molecular explanation for the recessive nature of autosomal recessive juvenile Parkinsonism.
Journal ArticleDOI
Autophagy induction as a therapeutic strategy for neurodegenerative diseases
TL;DR: Evidence in cells and in vivo demonstrates promising results in many disease models, in which autophagy upregulation is able to reduce the levels of toxic proteins, ameliorate signs of disease, and delay disease progression.
Journal ArticleDOI
Emerging role of mitophagy in human diseases and physiology
Jee-Hyun Um,Jeanho Yun +1 more
TL;DR: A better understanding of mitophagy will provide insights about human disease and offer novel chance for treatment, and recent studies showing the involvement ofMitophagy in differentiation and development, suggest thatmitophagy may play a more active role in controlling cellular functions.
Journal ArticleDOI
Parkinson’s disease: piecing together a genetic jigsaw
TL;DR: A review of advances in the genetics of Parkinson's disease, focusing on the monogenic forms and their clinical and population-genetic consequences, and a defect in another signalling pathway for mutations in NR4A2.
Journal ArticleDOI
Impaired dopamine release and synaptic plasticity in the striatum of Parkin−/− mice
Tohru Kitada,Antonio Pisani,Maha Karouani,Marian Haburcak,Giuseppina Martella,Anne Tscherter,Paola Platania,Bei Wu,Emmanuel N. Pothos,Jie Shen +9 more
TL;DR: Results indicate that Parkin is involved in the regulation of evoked dopamine release and striatal synaptic plasticity in the nigrostriatal pathway, and suggest that impairment in evoked serotonin release may represent a common pathophysiological change in recessive parkinsonism.
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
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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