The mTOR Signaling Pathway in Neurodegenerative Diseases

Abstract Neurodegenerative disorders are characterized by progressive accumulation of aggregated and misfolded proteins, brain inflammation, autophagy impairment, and metabolism disturbances associated with cognitive and/or physical declines. However, no therapy is available to stop the progression of major neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. The exact molecular mechanisms that govern these pathologies remain unclear. The mammalian target of rapamycin (mTOR) and its protein complexes, complex 1 (mTORC1) and complex 2 (mTORC2) offer exciting and unique avenues of intervention in these diseases through the oversight of programmed cell death pathways of apoptosis, autophagy, necroptosis, and cellular metabolism. With the ability of mTOR to broadly impact cellular function, clinical strategies for neurodegenerative disorders that implement mTOR must achieve parallel objectives to protect neuronal, vascular, and immune cell survival in conjunction with preserving networks that determine memory and cognitive function. This chapter presents for each disease the background of the mTOR signaling pathway in fundamental and clinical levels. In addition, data targeting mTOR in therapeutic strategies or as a biomarker are developed.