Protein clearance mechanisms and their demise in age-related neurodegenerative diseases

The accumulation of damaged proteins contributes to the etiology of neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's or amyotrophic lateral sclerosis. Protein aggregation and deposition are common features of these disorders that share emergence patterns and are more frequent late in life, even though different toxic proteins are involved in their onset. The ability to maintain a functional proteome, or proteostasis(definition), declines during the ageing process. Damaged proteins are degraded by the ubiquitin proteasome system or through autophagy(definition)-lysosome, key components of the proteostasis network. Here we review the links between neurodegenerative disorders and loss of protein clearance mechanisms with age.