Neurons affected in Alzheimer's disease (AD) experience mitochondrial dysfunction and a bioenergetic deficit that occurs early and promotes the disease-defining amyloid beta peptide (Aβ) and Tau pathologies. Emerging findings suggest that the autophagy/lysosome pathway that removes damaged mitochondria (mitophagy) is also compromised in AD, resulting in the accumulation of dysfunctional mitochondria. Results in animal and cellular models of AD and in patients with sporadic late-onset AD suggest that impaired mitophagy contributes to synaptic dysfunction and cognitive deficits by triggering Aβ and Tau accumulation through increases in oxidative damage and cellular energy deficits; these, in turn, impair mitophagy. Interventions that bolster mitochondrial health and/or stimulate mitophagy may therefore forestall the neurodegenerative process in AD.

中文翻译：

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线粒体自噬和阿尔茨海默病：细胞和分子机制


阿尔茨海默病 (AD) 中受影响的神经元会出现线粒体功能障碍和生物能缺陷，这些缺陷会在早期发生，并促进导致疾病的淀粉样蛋白 β 肽 (Aβ) 和 Tau 病理学。新发现表明，去除受损线粒体（线粒体自噬）的自噬/溶酶体途径在 AD 中也受到损害，导致功能失调的线粒体积累。 AD 动物和细胞模型以及散发性迟发性 AD 患者的结果表明，受损的线粒体自噬通过增加氧化损伤和细胞能量缺陷触发 Aβ 和 Tau 积累，从而导致突触功能障碍和认知缺陷。这些反过来又损害线粒体自噬。因此，促进线粒体健康和/或刺激线粒体自噬的干预措施可能会阻止 AD 的神经退行性过程。