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The Cast of Molecular Characters in Parkinson's Disease
Author(s) -
LIM KAH LEONG,
DAWSON VALINA L.,
DAWSON TED M.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb07465.x
Subject(s) - parkin , ubiquitin , pathogenesis , parkinson's disease , alpha synuclein , ubiquitin ligase , dopaminergic , disease , deubiquitinating enzyme , dopamine , pink1 , biology , microbiology and biotechnology , neuroscience , genetics , medicine , immunology , gene , pathology
A bstract : Parkinson's Disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopamine neurons and the accumulation of Lewy bodies and neurites. Recent advances indicate that PD is due in some individuals to genetic mutations in α‐synuclein, parkin, and ubiquitin C‐terminal hydrolase L1 (UCHL1). All three PD‐linked gene products are related directly or indirectly to the functioning of the cellular ubiquitin proteasomal system (UPS), suggesting that UPS dysfunction may be important in PD pathogenesis. Indeed, emerging evidence indicates that derangements of the UPS may be one of the underlying mechanisms of PD pathogenesis. The function of parkin as an ubiquitin protein ligase positions it as an important player in both familial and idiopathic PD. We recently demonstrated that parkin mediates a nondegradative form of ubiquitination on synphilin‐1 that could contribute to synphilin‐1's aggregation in PD. Our results implicate parkin involvement in the formation of Lewy bodies associated with sporadic PD. This review discusses the role of the UPS, as well as the modus operandi of the three PD candidate felons (α‐synuclein, parkin, and UCHL1) along with their conspirators in bringing about dopaminergic cell death in PD.