Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
Centre for Molecular Neurosciences, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
Cells. 2022 Dec 17;11(24):4111. doi: 10.3390/cells11244111.
Astrocytes are important for maintaining cholesterol metabolism, glutamate uptake, and neurotransmission. Indeed, inflammatory processes and neurodegeneration contribute to the altered morphology, gene expression, and function of astrocytes. Astrocytes, in collaboration with numerous microRNAs, regulate brain cholesterol levels as well as glutamatergic and inflammatory signaling, all of which contribute to general brain homeostasis. Neural electrical activity, synaptic plasticity processes, learning, and memory are dependent on the astrocyte-neuron crosstalk. Here, we review the involvement of astrocytic microRNAs that potentially regulate cholesterol metabolism, glutamate uptake, and inflammation in Alzheimer's disease (AD). The interaction between astrocytic microRNAs and long non-coding RNA and transcription factors specific to astrocytes also contributes to the pathogenesis of AD. Thus, astrocytic microRNAs arise as a promising target, as AD conditions are a worldwide public health problem. This review examines novel therapeutic strategies to target astrocyte dysfunction in AD, such as lipid nanodiscs, engineered G protein-coupled receptors, extracellular vesicles, and nanoparticles.
星形胶质细胞对于维持胆固醇代谢、谷氨酸摄取和神经递质传递非常重要。事实上，炎症过程和神经退行性变导致星形胶质细胞的形态、基因表达和功能发生改变。星形胶质细胞与众多 microRNAs 一起调节大脑中的胆固醇水平以及谷氨酰胺能和炎症信号，所有这些都有助于大脑的整体稳态。神经电活动、突触可塑性过程、学习和记忆都依赖于星形胶质细胞-神经元的相互作用。在这里，我们综述了星形胶质细胞 microRNAs 可能在阿尔茨海默病（AD）中调节胆固醇代谢、谷氨酸摄取和炎症的参与。星形胶质细胞 microRNAs 与长非编码 RNA 和特定于星形胶质细胞的转录因子的相互作用也有助于 AD 的发病机制。因此，星形胶质细胞 microRNAs 作为一个有前途的治疗靶点出现，因为 AD 是一个全球性的公共卫生问题。本综述探讨了针对 AD 中星形胶质细胞功能障碍的新型治疗策略，如脂质纳米盘、工程化 G 蛋白偶联受体、细胞外囊泡和纳米颗粒。
