Alteration in autophagic-lysosomal potential during ageing and neurological diseases: the microRNA perspective

Official URL: http://www.springer.com/medicine/pathology/journal/40139

Macroautophagy (shortly autophagy) is an evolutionary conserved degradation pathway that targets cytoplasmic substrates including long-lived proteins, protein aggregates and damaged organelles, and leads to their degradation in lysosomes. Beyond its role in adaptation to cellular stresses such as nutrient deprivation, hypoxia and toxins; recent studies attributed a central role to autophagy in aging and lifespan determination. Moreover, alterations and abnormalities of autophagy may contribute to a number of important health problems, including cancer, myopathies, metabolic disorders, and the focus of this review, ageing-related neurodegenerative diseases. Some disease-related, mutant and aggregation-prone proteins may be cleared by autophagy, on the other hand, disregulation of the autophagy pathways may also contribute to neurotoxicity observed in degenerative pathologies. microRNAs (miRNAs) are endogenous regulators of gene expression, and their deregulation was reported in several ageing-related conditions. Studies in the last few years introduced miRNAs as novel and potent regulators of autophagy. In this review article, we will summarize the connection between autophagy, ageing and Alzheimer’s, Parkinson’s and Huntington’s diseases, and discuss the role of autophagy-related miRNAs in this context.