Precise assembly and regulation of 26S proteasome and correlation between proteasome dysfunction and neurodegenerative diseases.
Neurodegenerative diseases (NDs) often involve the formation of abnormal and toxic protein aggregates, which are thought to be the primary factor in ND occurrence and progression. Aged neurons exhibit marked increases in aggregated protein levels, which can lead to increased cell death in specific brain regions. As no specific drugs/therapies for treating the symptoms or/and progression of NDs are available, obtaining a complete understanding of the mechanism underlying the formation of protein aggregates is needed for designing a novel and efficient removal strategy. Intracellular proteolysis generally involves either the lysosomal or ubiquitin-proteasome system. In this review, we focus on the structure and assembly of the proteasome, proteasome-mediated protein degradation, and the multiple dynamic regulatory mechanisms governing proteasome activity. We also discuss the plausibility of the correlation between changes in proteasome activity and the occurrence of NDs. [BMB Reports 2016; 49(9): 459-473].
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Eunju
E
Im
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Kwang Chul
KC
Chung
D001105:Archaea / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D058207:Sumoylation; D054875:Ubiquitination
D021122:Protein Subunits; D046988:Proteasome Endopeptidase Complex; C119011:26S proteasome non-ATPase regulatory subunit 13