ABSTRACT
Brain aging, defined as decline in brain function as a result of biological aging, is closely associated with lysosomal dysfunction. Changes in the numbers and enzymatic activities of lysosomes appear early during brain aging process; these changes appear to be common in several species of mammals and occur specifically in brain regions that are vulnerable to pathogenesis in age-related neurodegenerative diseases, including Alzheimer’s disease (AD). The present review first summarizes the correlative and experimental evidence for lysosomal dysfunction in brain aging and age-related neurodegeneration, then assesses the roles of lysosomal dysfunction in trophic factor signaling and in glia-mediated inflammation. Finally, the potential pathways through which lysosomal dysfunction induces neurodegeneration are outlined so as to provide novel avenues for therapeutic approaches for age-related neurodegeneration.
