Targeting autophagy in the brain: a promising approach?
Macroautophagy is an evolutionarily conserved lysosomal-dependent pathway of degradation of several cytoplasmic components, such as misfolded proteins or damaged organelles. This process of cellular self-digestion is involved in a number of physiological processes like survival, differentiation and development. The failure in the normal flow of the autophagic process has been associated with normal brain aging and with late-onset neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases. A common characteristic between these disorders is the accumulation of protein deposits composed by aberrant protein aggregates. Also dysfunctional organelles, particularly mitochondria, have been implicated in the pathophysiology of several neurodegenerative diseases. Here we give an overview of the importance of autophagy in brain aging and in age-related neurodegeneration. Furthermore, we will discuss autophagy as a potential therapeutic target to mitigate the adverse effects of aging and age-related diseases on brain function.
Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra, Portugal.
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Santos
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Cardoso
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Correia
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Carvalho
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Santos
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D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001921:Brain / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D006816:Huntington Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D013312:Stress, Physiological