Bi Wangyu, Lei Tong, Cai Shanglin, Zhang Xiaoshuang, Yang Yanjie, Xiao Zhuangzhuang, Wang Lei, Du Hongwu
School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China.
School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China; Daxing Research Institute, University of Science and Technology Beijing, China.
Int Immunopharmacol. 2022 Dec;113(Pt A):109368. doi: 10.1016/j.intimp.2022.109368. Epub 2022 Oct 29.
As the most common neurodegenerative disease, Alzheimer's disease (AD) exhibits an incomprehensible pathogenesis, which has led to the continuous failure of drug development in recent years. Although neuronal damage is considered a pathological feature of AD, treatment strategies targeting β-amyloid (Aβ) have not achieved beneficial effects. In-depth research on glial cells has revealed the strong importance and application prospects of astrocytes in the recovery of cognitive functions. This review summarizes the role of astrocytes in AD and the possibility of therapeutic strategies targeting astrocytes. Astrocytes are involved in brain lipid metabolism and can regulate the synthesis and degradation of Aβ to affect the pathology of AD. The tau protein is phosphorylated by astrocytes, and this phosphorylation leads to the formation of neurofibrillary tangles (NFTs). Astrocytes can express a variety of receptors and inflammatory factors and participate in the neuroinflammatory process and the release of proinflammatory mediators. When the glutamate produced by the neurons is not cleared by astrocytes, neurons undergo apoptosis due to blocked cell metabolism. Therapies for astrocytes are highly efficient, and these include stem cell therapy, gene editing technology, astrocyte transformation and chemical drugs. Here, we discuss the advantages and disadvantages of animal and cell models applied to the study of targeted astrocyte therapies. This study helps elucidate the mechanism of astrocytes in AD and promotes the clinical application of potential therapeutic strategies targeting astrocytes.
作为最常见的神经退行性疾病，阿尔茨海默病（AD）的发病机制尚不明确，这导致近年来药物研发不断失败。尽管神经元损伤被认为是AD的病理特征，但针对β-淀粉样蛋白（Aβ）的治疗策略并未取得有益效果。对胶质细胞的深入研究揭示了星形胶质细胞在认知功能恢复中的重要作用和应用前景。本文综述了星形胶质细胞在AD中的作用以及针对星形胶质细胞的治疗策略的可能性。星形胶质细胞参与脑脂质代谢，并可调节Aβ的合成与降解以影响AD的病理过程。tau蛋白可被星形胶质细胞磷酸化，这种磷酸化导致神经原纤维缠结（NFTs）的形成。星形胶质细胞可表达多种受体和炎症因子，并参与神经炎症过程和促炎介质的释放。当神经元产生的谷氨酸不能被星形胶质细胞清除时，神经元会因细胞代谢受阻而发生凋亡。针对星形胶质细胞的治疗方法效率很高，包括干细胞治疗、基因编辑技术、星形胶质细胞转化和化学药物。在此，我们讨论了应用于靶向星形胶质细胞治疗研究的动物和细胞模型的优缺点。本研究有助于阐明星形胶质细胞在AD中的作用机制，并促进针对星形胶质细胞的潜在治疗策略在临床上的应用。
