Ubiquitin-Proteasome-Mediated Protein Degradation and Disorders of the Central Nervous System
Ashok N. Hegde, Logan E. Timm, Connor J. Sivley, Shrenik Ramiyaramcharankarthic, Olivia J. Lowrimore, Brenna J. Hendrix, Teodora G. Grozdanov, W. J. Anderson
Abstract
Ubiquitin-proteasome-mediated proteolysis post-translationally regulates the amounts of many proteins that are critical for the normal physiology of the central nervous system. Research carried out over the last several years has revealed a role for components of the ubiquitin-proteasome pathway (UPP) in many neurodegenerative diseases such as Parkinson's disease and Huntington's disease. Studies have also shown a role for the UPP in mental disorders such as schizophrenia and autism. Even though dysregulation of protein degradation by the UPP is a contributory factor to the pathology underlying many nervous system disorders, the association between the components of the UPP and these diseases is far from simple. In this review, we discuss the connections between the UPP and some of the major mental disorders and neurodegenerative diseases.