Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada.
Centre for Neuroscience, Brock University, St. Catharines, ON L2S 3A1, Canada.
Int J Mol Sci. 2021 Apr 28;22(9):4628. doi: 10.3390/ijms22094628.
Alzheimer's disease (AD) has traditionally been discussed as a disease where serious cognitive decline is a result of A-plaque accumulation, tau tangle formation, and neurodegeneration. Recently, it has been shown that metabolic dysregulation observed with insulin resistance and type-2 diabetes actively contributes to the progression of AD. One of the pathologies linking metabolic disease to AD is the release of inflammatory cytokines that contribute to the development of brain neuroinflammation and mitochondrial dysfunction, ultimately resulting in amyloid-beta peptide production and accumulation. Improving these metabolic impairments has been shown to be effective at reducing AD progression and improving cognitive function. The polyphenol resveratrol (RSV) improves peripheral metabolic disorders and may provide similar benefits centrally in the brain. RSV reduces inflammatory cytokine release, improves mitochondrial energetic function, and improves A-peptide clearance by activating SIRT1 and AMPK. RSV has also been linked to improved cognitive function; however, the mechanisms of action are less defined. However, there is evidence to suggest that chronic RSV-driven AMPK activation may be detrimental to synaptic function and growth, which would directly impact cognition. This review will discuss the benefits and adverse effects of RSV on the brain, highlighting the major signaling pathways and some of the gaps surrounding the use of RSV as a treatment for AD.
阿尔茨海默病（AD）传统上被认为是一种疾病，其严重认知能力下降是由于 A 斑块积累、tau 缠结形成和神经退行性变所致。最近，已经表明胰岛素抵抗和 2 型糖尿病引起的代谢失调会积极促进 AD 的进展。将代谢疾病与 AD 联系起来的一种病理学是炎症细胞因子的释放，炎症细胞因子会导致脑神经炎症和线粒体功能障碍的发展，最终导致淀粉样β肽的产生和积累。已经证明，改善这些代谢异常可以有效减缓 AD 的进展并改善认知功能。多酚白藜芦醇（RSV）可以改善外周代谢紊乱，并可能在大脑中提供类似的益处。RSV 通过激活 SIRT1 和 AMPK 来减少炎症细胞因子的释放、改善线粒体能量功能以及促进 A 肽的清除。RSV 也与改善认知功能有关；然而，其作用机制尚不清楚。但是，有证据表明，慢性 RSV 驱动的 AMPK 激活可能对突触功能和生长有害，这将直接影响认知。本综述将讨论 RSV 对大脑的益处和不良反应，重点介绍主要的信号通路以及围绕 RSV 作为 AD 治疗方法的一些空白。
