Physiological and Pathological Role of mTOR Signaling in Astrocytes

Abstract

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.