Alzheimer's disease: a lesson from mitochondrial dysfunction.
Extensive literature exists supporting a role for mitochondrial dysfunction and oxidative damage in the pathogenesis of Alzheimer's disease. Mitochondria are a major source of intracellular reactive oxygen species and are particularly vulnerable to oxidative stress. This review discusses evidence supporting the notion that mitochondrial dysfunction is intimately associated with Alzheimer's disease pathogenesis. Furthermore, the potential connection between mitochondrial dysfunction/oxidative stress and autophagy in Alzheimer's disease is also discussed. As a result of insufficient digestion of oxidatively damaged macromolecules and organelles by autophagy, neurons progressively accumulate lipofuscin (biological garbage) that could exacerbate neuronal dysfunction. The knowledge that mitochondrial dysfunction has a preponderant role in several pathological conditions instigated the development of mitochondrial antioxidant therapies. Mitochondria-targeted antioxidant treatments are briefly discussed in this review.
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Paula I
PI
Moreira
Maria S
MS
Santos
Catarina R
CR
Oliveira
D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology*; D000975:Antioxidants / Q000494:pharmacology; D001343:Autophagy; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress
D000975:Antioxidants