The impact of proteostasis dysfunction secondary to environmental and genetic causes on neurodegenerative diseases progression and potential therapeutic intervention

Abstract

Aggregation of particular proteins in the form of inclusion bodies or plaques followed by neuronal death is a hallmark of neurodegenerative proteopathies such as primary Parkinsonism, Alzheimer’s disease, Lou Gehrig’s disease, and Huntington’s chorea. Complex polygenic and environmental factors implicated in these proteopathies. Accumulation of proteins in these disorders indicates a substantial disruption in protein homeostasis (proteostasis). Proteostasis or cellular proteome homeostasis is attained by the synchronization of a group of cellular mechanisms called the proteostasis network (PN), which is responsible for the stability of the proteome and achieves the equilibrium between synthesis, folding, and degradation of proteins. In this review, we will discuss the different types of PN and the impact of PN component dysfunction on the four major neurodegenerative diseases mentioned earlier. [Figure not available: see fulltext.]