Ubiquitin and Intracellular Aggregation

The ubiquitin-proteasome system (UPS) is involved in many biological pathways via the degradation of short-lived and regulatory proteins important in cellular processes. Moreover, in the most of the chronic human neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), protein aggregation co-localized with ubiquitin is a common feature and may be caused by the abrogation of UPS. Parkin gene isolated from autosomal recessive-juvenile parkinsonism (AR-JP) is ubiquitin-protein ligase (E3) and many mutations of parkin in familial PD disrupted the ubiquitin-protein ligase activity to eventually accumulate its substrates in intracellular aggresome (Lewy body). Pathogenic proteins of AD, including presenilin and Amyloid-b Precursor Protein (APP), are the substrates of UPS and the mutations related with AD pathogenesis give resistance to their degradation by proteasome. Therefore, UPS is the important target of therapeutic trial for neurodegenerative disorders.