Linked Life Data

20221696

Source:http://linkedlifedata.com/resource/pubmed/id/20221696

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-11-12
pubmed:abstractText
Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder beyond Alzheimer's disease, affecting approximately 1% of people over the age of 65. The major pathological hallmarks of PD are significant loss of nigrostriatal dopaminergic (DA) neurons and the presence of intraneuronal protein inclusions termed Lewy bodies. Sporadic cases represent more than 90% of total patients with PD, while there exist several inherited forms caused by mutations in single genes. Identification and characterization of these causative genes and their products can help us understand the molecular mechanisms of DA neuronal cell death and design new approaches to treat both the inherited and sporadic forms of PD. Based on the finding that a point mutation in the gene encoding ?-synuclein (?Syn) protein causes a rare familial form of PD, PARK1, it is now confirmed that ?Syn is a major component of Lewy bodies in patients with sporadic PD. Abnormal accumulation of ?Syn protein is considered a neurotoxic event in the development of PD. PARK4, another dominantly inherited form of familial PD, is caused by duplication or triplication of the ?Syn gene locus. This genetic mutation results in the production of large amounts of wild-type ?Syn protein, supporting the ?Syn-induced neurodegeneration hypothesis. On the other hand, the recessively inherited early-onset Parkinsonism is caused in about half of the cases with loss-of-function mutations in PARK2, which encodes E3 ubiquitin ligase parkin in the ubiquitin-proteasome system. These findings have shed light on DA neurodegeneration caused by accumulation of toxic protein species that can be degraded and/or detoxicated through parkin activity. In this review, we will focus on the regulatory roles of ?Syn and parkin proteins in DA neuronal cell apoptosis and provide evidence for the possible therapeutic action of parkin in sporadic patients with PD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1573-675X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1312-21
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The regulatory role of ?-synuclein and parkin in neuronal cell apoptosis; possible implications for the pathogenesis of Parkinson's disease.
pubmed:affiliation
Department of Neurology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. tyasuda@med.kitasato-u.ac.jp
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't