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.
Bibliographical noteFunding Information:
This research was supported by grants from the National Research Foundation of Korea (NRF) (2015R1A2A2A01003 080 and 2014M3C7A1064545 to KCC) funded by the Ministry of Science, ICT & Future Planning (MSIP), Republic of Korea, and by grant from the Korea Healthcare Technology R&D Project (HI14C0093 to KCC) through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea. This work was also supported in part by the Yonsei University Research Fund of 2014 (2014-12-0134 to EI), and by the Yonsei University Future-leading Research Initiative of 2015 (2015-22-0055 to KCC).
All Science Journal Classification (ASJC) codes
- Molecular Biology