Mitroshina Elena, Kalinina Elizaveta, Vedunova Maria
Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Avenue, 603022 Nizhny Novgorod, Russia.
Antioxidants (Basel). 2023 Oct 13;12(10):1856. doi: 10.3390/antiox12101856.
Alzheimer's disease (AD) is the most common form of dementia, resulting in disability and mortality. The global incidence of AD is consistently surging. Although numerous therapeutic agents with promising potential have been developed, none have successfully treated AD to date. Consequently, the pursuit of novel methodologies to address neurodegenerative processes in AD remains a paramount endeavor. A particularly promising avenue in this search is optogenetics, enabling the manipulation of neuronal activity. In recent years, research attention has pivoted from neurons to glial cells. This review aims to consider the potential of the optogenetic correction of astrocyte metabolism as a promising strategy for correcting AD-related disorders. The initial segment of the review centers on the role of astrocytes in the genesis of neurodegeneration. Astrocytes have been implicated in several pathological processes associated with AD, encompassing the clearance of β-amyloid, neuroinflammation, excitotoxicity, oxidative stress, and lipid metabolism (along with a critical role in apolipoprotein E function). The effect of astrocyte-neuronal interactions will also be scrutinized. Furthermore, the review delves into a number of studies indicating that changes in cellular calcium (Ca) signaling are one of the causes of neurodegeneration. The review's latter section presents insights into the application of various optogenetic tools to manipulate astrocytic function as a means to counteract neurodegenerative changes.
阿尔茨海默病(AD)是最常见的痴呆形式,会导致残疾和死亡。全球AD发病率持续飙升。尽管已经开发出许多具有潜在前景的治疗药物,但迄今为止尚无一种能成功治疗AD。因此,寻求解决AD神经退行性过程的新方法仍然是一项至关重要的工作。在这一探索中,一个特别有前景的途径是光遗传学,它能够操纵神经元活动。近年来,研究重点已从神经元转向神经胶质细胞。本综述旨在探讨光遗传学纠正星形胶质细胞代谢作为纠正AD相关疾病的一种有前景策略的潜力。综述的第一部分聚焦于星形胶质细胞在神经退行性变发生中的作用。星形胶质细胞与AD相关的几种病理过程有关,包括β-淀粉样蛋白的清除、神经炎症、兴奋性毒性、氧化应激和脂质代谢(以及在载脂蛋白E功能中起关键作用)。还将详细研究星形胶质细胞与神经元相互作用的影响。此外,综述深入探讨了一些研究,这些研究表明细胞钙(Ca)信号的变化是神经退行性变的原因之一。综述的后半部分介绍了各种光遗传学工具在操纵星形胶质细胞功能以对抗神经退行性变化方面的应用见解。