Neurogenetics Laboratory, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
Brain Res. 2011 Sep 30;1415:136-48. doi: 10.1016/j.brainres.2011.07.052. Epub 2011 Jul 31.
Growing evidence suggests that amyloid beta (Aβ) and tau pathologies are strongly associated with mitochondrial dysfunction and neuronal damage in Alzheimer's disease (AD). Extensive research of AD postmortem brains, mouse and fly models, including triple transgenic AD mice and mutant tau mice, and cell culture studies revealed that tau hyperphosphorylation is caused by multiple factors, including intraneuronal Aβ-oligomers, chronic oxidative stress, reduced insulin-like growth factor 1, and astrocytic mediated-Aβ and caspase activation. Overexpressed and phosphorylated tau appears to impair axonal transport of organelles causing synapse starvation, depletion of ATP, and ultimately neuronal damage. This article evaluates the role of tau in mitochondrial dysfunction and assesses how hyperphosphorylated tau impairs axonal transport of organelles in AD neurons.
越来越多的证据表明，淀粉样蛋白β（Aβ）和 tau 病理学与阿尔茨海默病（AD）中的线粒体功能障碍和神经元损伤密切相关。对 AD 尸检大脑、小鼠和果蝇模型（包括三转基因 AD 小鼠和突变 tau 小鼠）以及细胞培养研究的广泛研究表明，tau 过度磷酸化是由多种因素引起的，包括神经元内 Aβ-寡聚物、慢性氧化应激、胰岛素样生长因子 1 减少以及星形胶质细胞介导的 Aβ和半胱天冬酶激活。过度表达和磷酸化的 tau 似乎会损害细胞器的轴突运输，导致突触饥饿、ATP 耗竭，最终导致神经元损伤。本文评估了 tau 在线粒体功能障碍中的作用，并评估了过度磷酸化的 tau 如何损害 AD 神经元中细胞器的轴突运输。
