Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin

Sep 18, 2012Progress in neurobiology

New insights into brain diseases caused by cell damage through the mTOR pathway

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Abstract

Neurodegenerative disorders impact nearly 30 million individuals worldwide, leading to significant disability or death.

The mammalian target of rapamycin (mTOR) is a potential therapeutic target for various neurodegenerative diseases, including Alzheimer's and Parkinson's.
mTOR signaling involves two complexes, mTORC1 and mTORC2, which interact with several regulatory proteins.
mTOR can promote processes such as stem cell proliferation, tissue repair, and synaptic growth while also influencing cell death and recycling mechanisms.
The proliferative effects of mTOR may hinder recovery in the central nervous system and could contribute to tumor development.
Understanding mTOR and its signaling pathways may lead to new treatment options for neurodegenerative disorders.

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Neurodegenerative disorders affect a significant portion of the world's population leading to either disability or death for almost 30 million individuals worldwide. One novel therapeutic target that may offer promise for multiple disease entities that involve Alzheimer's disease, Parkinson's disease, epilepsy, trauma, stroke, and tumors of the nervous system is the mammalian target of rapamycin (mTOR). mTOR signaling is dependent upon the mTORC1 and mTORC2 complexes that are composed of mTOR and several regulatory proteins including the tuberous sclerosis complex (TSC1, hamartin/TSC2, tuberin). Through a number of integrated cell signaling pathways that involve those of mTORC1 and mTORC2 as well as more novel signaling tied to cytokines, Wnt, and forkhead, mTOR can foster stem cellular proliferation, tissue repair and longevity, and synaptic growth by modulating mechanisms that foster both apoptosis and autophagy. Yet, mTOR through its proliferative capacity may sometimes be detrimental to central nervous system recovery and even promote tumorigenesis. Further knowledge of mTOR and the critical pathways governed by this serine/threonine protein kinase can bring new light for neurodegeneration and other related diseases that currently require new and robust treatments.

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Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin

Abstract

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