Can Co-Activation of Nrf2 and Neurotrophic Signaling Pathway Slow Alzheimer's Disease?
Can Co-Activation of Nrf2 and Neurotrophic Signaling Pathway Slow Alzheimer's Disease?
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DOI：
10.3390/ijms18061168
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发表时间：
2017-05-31
影响因子：
5.6
通讯作者：
Park JJ
中科院分区：
文献类型：
--
作者：
Murphy KE;Park JJ
阿尔茨海默病（AD）是一种多方面的疾病，很难通过单一模式治疗。AD的发病机制从淀粉样肽、线粒体功能障碍和氧化应激开始，到后来伴有慢性内质网应激和自噬功能障碍，其发病机制更为复杂。目前，很少有治疗方法可以改变AD复杂的发病过程。与外源性抗氧化剂治疗相比，通过Nrf2激活整体抗氧化防御系统似乎更有希望减轻AD脑中的氧化应激。伴随着Nrf2介导的抗氧化防御系统的激活，减少AD的致病因素，氧化应激，也有必要激活神经营养信号通路，用新的细胞器和分子取代受损的细胞器和分子。因此，激活Nrf2抗氧化系统和神经营养信号通路的双重作用有望为改变AD发病机制提供更好的策略。本文综述了近年来对AD发病机制和神经防御系统的研究进展，并探讨了协同激活Nrf2抗氧化系统和神经营养信号通路的可能途径，以期为延缓AD的发病提供新的思路。
Alzheimer’s disease (AD) is a multifaceted disease that is hard to treat by single-modal treatment. AD starts with amyloid peptides, mitochondrial dysfunction, and oxidative stress and later is accompanied with chronic endoplasmic reticulum (ER) stress and autophagy dysfunction, resulting in more complicated pathogenesis. Currently, few treatments can modify the complicated pathogenic progress of AD. Compared to the treatment with exogenous antioxidants, the activation of global antioxidant defense system via Nrf2 looks more promising in attenuating oxidative stress in AD brains. Accompanying the activation of the Nrf2-mediated antioxidant defense system that reduce the AD-causative factor, oxidative stress, it is also necessary to activate the neurotrophic signaling pathway that replaces damaged organelles and molecules with new ones. Thus, the dual actions to activate both the Nrf2 antioxidant system and neurotrophic signaling pathway are expected to provide a better strategy to modify AD pathogenesis. Here, we review the current understanding of AD pathogenesis and neuronal defense systems and discuss a possible way to co-activate the Nrf2 antioxidant system and neurotrophic signaling pathway with the hope of helping to find a better strategy to slow AD.