在阿尔茨海默病转基因小鼠模型中,跑步机运动可缓解大脑铁失衡,加速神经元淀粉样蛋白-β的生成、神经元细胞死亡和认知障碍

Dong-Hun Choi, Ki-chun Kwon, Dong-Ju Hwang, Hyun-Seob Um, Jung‐hoon Koo, Eung-Jun Kim, D. Yeom, Joon-Yong Cho
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引用次数: 0

摘要

脑铁会随着年龄的增长而增加,事实证明,脑铁失衡越来越有可能与阿尔茨海默病(AD)和帕金森病(PD)的病理有关,可能是通过促进氧化损伤造成的。因此,迫切需要研究改善铁在阿尔茨海默病中的作用。持续运动或许是减缓铁超载速度的一种方法,因为它可以减轻芬顿反应引起的氧化应激。然而,运动对铁毒性影响的确切机制尚不十分清楚。在此,我们利用 APP-C105 AD 模型小鼠,探讨了跑步机运动是否会影响体内脑铁状态的 AD 相关机制。在 APP-C105 AD 模型小鼠中,我们观察到铁诱导的淀粉样前体蛋白(APP)加工、神经元凋亡信号传导、氧化应激和认知障碍的破坏。此外,跑步机运动阻断了与Aβ诱导的神经元细胞死亡(可能是通过APP错误处理)、氧化应激和认知功能下降相关的脑铁失衡,这表明跑步机运动通过促进非淀粉样蛋白生成途径(可能是通过增强嘌呤)缓解了Aβ诱导的神经元细胞死亡和认知功能下降,同时抑制了氧化应激(可能是通过下调脑铁失衡)。综上所述,我们有证据表明,跑步机运动可通过增强嘌呤上调非淀粉样蛋白生成途径,同时下调铁介导的氧化应激,从而抑制Aβ诱导的神经元细胞死亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Treadmill exercise alleviates brain iron dyshomeostasis accelerating neuronal amyloid‐β production, neuronal cell death and cognitive impairment in transgenic mice model of Alzheimer’s disease
Brain iron increases with age and brain iron dyshomeostasis is proving increasingly likely to be involved in the pathology of Alzheimer’s disease (AD) and Parkinson’s disease (PD), possibly via promoting oxidative damage. There is therefore an urgent need to research into improving role iron play in AD. Sustained exercise may be ways to slow the rate of overload of iron, by perhaps alleviating oxidative stress due to the Fenton reaction. Yet, the exact mechanisms of the effects of exercise on iron toxicity are not well understood. Here, we explored whether treadmill exercise impacts the AD‐related mechanism(s) of brain iron status in vivo, using APP‐C105 AD‐model mice. We observed iron‐induced disruptions of amyloid precursor protein (APP) processing, neuronal apoptotic signaling, oxidative stress, and cognitive impairment in APP‐C105 AD‐model mice. Further, brain iron dyshomeostasis associated with Aβ‐induced neuronal cell death possibly via APP misprocessing, and oxidative stress and cognitive decline was blocked by treadmill exercise, suggesting effect led to mitigated Aβ‐induced neuronal cell death and cognitive decline by promoting non‐amyloidogenic pathway possibly via enhanced furin, concomitant with inhibiting oxidative stress possibly via down‐regulating brain iron dyshomeostasis. Together, we show evidences to suggest that treadmill exercise may be ways to inhibit Aβ‐induced neuronal cell death by up‐regulating non‐amyloidogenic pathway through enhanced furin, concomitant with down‐regulating iron‐mediated oxidative stress.
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