Hochmuth Luise, Hirrlinger Johannes
Carl-Ludwig-Institute for Physiology, Faculty of Medicine, University of Leipzig, D- 04103, Leipzig, Germany.
Department of Neurogenetics, Max-Planck-Institute for Multidisciplinary Sciences, D- 37075, Göttingen, Germany.
Neurochem Res. 2024 Dec 9;50(1):53. doi: 10.1007/s11064-024-04306-6.
The mammalian target of rapamycin (mTOR) signaling pathway is one of the key regulators of cellular energy metabolism. It senses diverse alterations in the extracellular environment such as availability of nutrients and growth factors, and mediates the corresponding intracellular response. In the brain, astrocytes crucially contribute to energy and neurotransmitter metabolism, and numerous other functions. However, the relevance of physiological, astrocytic mTOR signaling in maintaining brain homeostasis and function is not well understood. Pathophysiological mTOR signaling is involved in manifold diseases in the central nervous system and most of the knowledge about astrocytic mTOR signaling has been derived from observations on these disorders. Dysregulation of the mTOR signaling pathway impairs important functions of astrocytes including neurotransmitter uptake and -signaling as well as energy metabolism. Some of these alterations could trigger neuropathological conditions such as epilepsy. This review focuses on how mTOR signaling regulates properties of astrocytes, and how these signaling events might contribute to the physiological function of the brain.
雷帕霉素哺乳动物靶蛋白(mTOR)信号通路是细胞能量代谢的关键调节因子之一。它能感知细胞外环境中的多种变化,如营养物质和生长因子的可用性,并介导相应的细胞内反应。在大脑中,星形胶质细胞对能量和神经递质代谢以及许多其他功能起着至关重要的作用。然而,生理状态下星形胶质细胞的mTOR信号在维持大脑稳态和功能中的相关性尚未得到充分理解。病理生理状态下的mTOR信号参与中枢神经系统的多种疾病,并且关于星形胶质细胞mTOR信号的大多数知识都来自于对这些疾病的观察。mTOR信号通路的失调会损害星形胶质细胞的重要功能,包括神经递质摄取和信号传递以及能量代谢。其中一些改变可能引发神经病理状况,如癫痫。本综述重点关注mTOR信号如何调节星形胶质细胞的特性,以及这些信号事件可能如何对大脑的生理功能做出贡献。