A synergistic dysfunction of mitochondrial fission/fusion dynamics and mitophagy in Alzheimer's disease.
Alzheimer's disease (AD), the most common form of dementia in the elderly, can have a late-onset sporadic or an early-onset familial origin. In both cases, the neuropathological hallmarks are the same: senile plaques and neurofibrillary tangles. Despite AD having a proteinopathic nature, there is strong evidence for an organelle dysfunction-related neuropathology, namely dysfunctional mitochondria. In this regard, dysfunctional mitochondria and associated exacerbated generation of reactive oxygen species are among the earliest events in the progression of the disease. Since the maintenance of a healthy mitochondrial pool is essential given the central role of this organelle in several determinant cellular processes, mitochondrial dysfunction in AD would be predicted to have profound pluripotent deleterious consequences. Mechanistically, recent reports suggest that mitochondrial fission/fusion and mitophagy are altered in AD and in in vitro models of disease, and since both processes are reported to be protective, this review will discuss the role of mitochondrial fission/fusion and mitophagy in the pathogenesis of AD.
Santos
Renato X
RX
Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, Coimbra, Portugal.
Correia
Sónia C
SC
Wang
Xinglong
X
Perry
George
G
Smith
Mark A
MA
Moreira
Paula I
PI
Zhu
Xiongwei
X
D000544:Alzheimer Disease / Q000209:etiology*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000473:pathology / Q000502:physiology; D028361:Mitochondrial Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological
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