Ubiquitin-proteasome system and Parkinson's diseases.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by nigrostriatal dopaminergic degeneration and development of cytoplasmic inclusions known as Lewy bodies. To date, the mechanisms involved in PD pathogenesis are not clearly understood. Clues from genetic studies including identification of mutations in genes for alpha-synuclein, parkin, and ubiquitin carboxy hydrolase L1 associated with familial PD and the presence of proteinaceous cytoplasmic inclusions in spared dopaminergic nigral neurons in sporadic cases of PD have suggested an important role for ubiquitin-proteasome system (UPS) and aberrant protein degradation. In vivo and in vitro studies have linked parkin, alpha-synuclein, and oxidative stress to a compromised UPS and PD pathogenesis suggesting novel therapeutic targets.
Betarbet
Ranjita
R
Center for Neurodegenerative Disease, Department of Neurology, Emory University, Atlanta, GA 30322, USA. rbetarb@emory.edu
Sherer
Todd B
TB
Greenamyre
J Timothy
JT
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051843:Synucleins; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D025801:Ubiquitin; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex