Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia.
Cooperative Research Centre for Mental Health, Carlton, VIC 3053, Australia.
Nutrients. 2021 Oct 23;13(11):3744. doi: 10.3390/nu13113744.
Mitochondrial dysfunction including deficits of mitophagy is seen in aging and neurodegenerative disorders including Alzheimer's disease (AD). Apart from traditionally targeting amyloid beta (Aβ), the main culprit in AD brains, other approaches include investigating impaired mitochondrial pathways for potential therapeutic benefits against AD. Thus, a future therapy for AD may focus on novel candidates that enhance optimal mitochondrial integrity and turnover. Bioactive food components, known as nutraceuticals, may serve as such agents to combat AD. Urolithin A is an intestinal microbe-derived metabolite of a class of polyphenols, ellagitannins (ETs). Urolithin A is known to exert many health benefits. Its antioxidant, anti-inflammatory, anti-atherogenic, anti-Aβ, and pro-mitophagy properties are increasingly recognized. However, the underlying mechanisms of urolithin A in inducing mitophagy is poorly understood. This review discusses the mitophagy deficits in AD and examines potential molecular mechanisms of its activation. Moreover, the current knowledge of urolithin A is discussed, focusing on its neuroprotective properties and its potential to induce mitophagy. Specifically, this review proposes potential mechanisms by which urolithin A may activate and promote mitophagy.
线粒体功能障碍包括自噬缺陷，在衰老和神经退行性疾病中都有出现，包括阿尔茨海默病（AD）。除了传统上针对淀粉样蛋白β（Aβ）的治疗方法，Aβ是 AD 大脑中的主要罪魁祸首，其他方法还包括研究受损的线粒体途径，以寻找对抗 AD 的潜在治疗益处。因此，AD 的未来疗法可能集中在增强最佳线粒体完整性和周转率的新型候选药物上。生物活性食物成分，即功能性食品，可能成为对抗 AD 的此类药物。尿石素 A 是一类多酚、鞣花单宁（ETs）的肠道微生物衍生代谢物。已知尿石素 A 具有许多健康益处。其抗氧化、抗炎、抗动脉粥样硬化、抗 Aβ 和促进自噬的特性正日益得到认可。然而，尿石素 A 诱导自噬的潜在机制尚不清楚。本文综述了 AD 中的自噬缺陷，并探讨了其激活的潜在分子机制。此外，还讨论了尿石素 A 的现有知识，重点介绍其神经保护特性及其诱导自噬的潜力。具体来说，本文提出了尿石素 A 可能通过哪些机制激活和促进自噬的假说。
