mTOR signaling in neural stem cells: from basic biology to disease

• Published in: Cellular and molecular life sciences : CMLS Vol. 70; no. 16; pp. 2887 - 2898
• Main Authors: Magri, Laura, Galli, Rossella
• Format: Journal Article
• Language: English
• Published: Basel Springer-Verlag 01.08.2013; Springer Basel; Springer Nature B.V
• Subjects: Animal models; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; brain; Cell Biology; Cellular biology; hamartoma; Hamartoma Syndrome, Multiple - metabolism; Hamartoma Syndrome, Multiple - pathology; homeostasis; Humans; Life Sciences; mammals; metabolic diseases; Metabolic Diseases - metabolism; Metabolic Diseases - pathology; Metabolic disorders; Mutagenesis; neoplasms; Neoplasms - metabolism; Neoplasms - pathology; Neural Stem Cells - metabolism; Neural Stem Cells - pathology; Neurological disorders; Pathogenesis; Review; sclerosis; Signal Transduction; Stem cells; TOR Serine-Threonine Kinases - metabolism; mTOR; Neural stem cells; Tuberous sclerosis complex
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-012-1196-x

The mammalian target of rapamycin (mTOR) pathway is a central controller of growth and homeostasis, and, as such, is implicated in disease states where growth is deregulated, namely cancer, metabolic diseases, and hamartoma syndromes like tuberous sclerosis complex (TSC). Accordingly, mTOR is also a pivotal regulator of the homeostasis of several distinct stem cell pools in which it finely tunes the balance between stem cell self-renewal and differentiation. mTOR hyperactivation in neural stem cells (NSCs) has been etiologically linked to the development of TSC-associated neurological lesions, such as brain hamartomas and benign tumors. Animal models generated by deletion of mTOR upstream regulators in different types of NSCs reproduce faithfully some of the TSC neurological alterations. Thus, mTOR dysregulation in NSCs seems to be responsible for the derangement of their homeostasis, thus leading to TSC development. Here we review recent advances in the molecular dissection of the mTOR cascade, its involvement in the maintenance of stem cell compartments, and in particular the implications of mTOR hyperactivation in NSCs in vivo and in vitro.