Center for Mitochondrial Biology & Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Antioxid Redox Signal. 2020 Jun 1;32(16):1188-1236. doi: 10.1089/ars.2019.7763. Epub 2020 Mar 16.
Epidemiological studies indicate that metabolic disorders are associated with an increased risk for Alzheimer's disease (AD). Metabolic remodeling occurs in the central nervous system (CNS) and periphery, even in the early stages of AD. Mitochondrial dysfunction has been widely accepted as a molecular mechanism underlying metabolic disorders. Therefore, focusing on early metabolic changes, especially from the perspective of mitochondria, could be of interest for early AD diagnosis and intervention. We and others have identified that the levels of several metabolites are fluctuated in the periphery before their accumulation in the CNS, which plays an important role in the pathogenesis of AD. Mitochondrial remodeling is likely one of the earliest signs of AD, linking nutritional imbalance to cognitive deficits. Notably, by improving mitochondrial function, mitochondrial nutrients efficiently rescue cellular metabolic dysfunction in the CNS and periphery in individuals with AD. Peripheral metabolic disorders should be intensively explored and evaluated for the early diagnosis of AD. The circulating metabolites derived from mitochondrial remodeling represent novel potential diagnostic biomarkers for AD that are more readily detected than CNS-oriented biomarkers. Moreover, mitochondrial nutrients provide a promising approach to preventing and delaying AD progression. Abnormal mitochondrial metabolism in the CNS and periphery is involved in AD pathogenesis. More clinical studies provide evidence for the suitability and reliability of circulating metabolites and cytokines for the early diagnosis of AD. Targeting mitochondria to rewire cellular metabolism is a promising approach to preventing AD and ameliorating AD-related metabolic disorders.
流行病学研究表明，代谢紊乱与阿尔茨海默病（AD）的风险增加有关。代谢重塑发生在中枢神经系统（CNS）和外周，甚至在 AD 的早期阶段也是如此。线粒体功能障碍已被广泛认为是代谢紊乱的分子机制。因此，关注早期代谢变化，特别是从线粒体的角度来看，可能有助于 AD 的早期诊断和干预。 我们和其他人已经发现，在这些代谢物在 CNS 中积累之前，其在周围的水平就已经波动了，这在 AD 的发病机制中起着重要作用。线粒体重塑可能是 AD 的最早迹象之一，将营养失衡与认知缺陷联系起来。值得注意的是，通过改善线粒体功能，线粒体营养素可以有效地挽救 AD 个体 CNS 和外周的细胞代谢功能障碍。 应该深入探索和评估外周代谢紊乱，以实现 AD 的早期诊断。源自线粒体重塑的循环代谢物代表了 AD 的新型潜在诊断生物标志物，比 CNS 为导向的生物标志物更容易检测到。此外，线粒体营养素为预防和延缓 AD 进展提供了一种有前途的方法。 CNS 和外周的异常线粒体代谢参与 AD 的发病机制。更多的临床研究为循环代谢物和细胞因子用于 AD 的早期诊断的适宜性和可靠性提供了证据。针对线粒体来重新布线细胞代谢是预防 AD 和改善 AD 相关代谢紊乱的一种很有前途的方法。
