Translation stalling and ribosome collision leading to proteostasis failure:implications for neurodegenerative diseases

摘要

Proteostasis denotes a cellular state in which protein synthesis,folding,and degradation are maintained at a homeostatic state such that an intact yet dynamic proteome is preserved.Cellular capacity to preserve proteostasis declines with age,which is assumed to contribute to the pathogenesis of age-related diseases.Proteostasis failure manifested as the formation of aberrant protein aggregates,including the amyloid plaques in Alzheimer’s disease(AD),Lewy bodies in Parkinson’s disease,and TAR DNA binging protein 43 inclusions in amyotrophic lateral sclerosis(ALS),is a defining feature of neurodegenerative diseases.