Cutting through the Complexities of mTOR for the Treatment of Stroke

On a global basis, at least 15 million individuals suffer some form of a stroke every year. Of these individuals, approximately 800,000 of these cerebrovascular events occur in the United States (US) alone. The incidence of stroke in the US has declined from the third leading cause of death to the fourth, a result that can be attributed to multiple factors that include improved vascular disease management, reduced tobacco use, and more rapid time to treatment in patients that are clinically appropriate to receive recombinant tissue plasminogen activator. However, treatment strategies for the majority of stroke patients are extremely limited and represent a critical void for care. A number of new therapeutic considerations for stroke are under consideration, but it is the mammalian target of rapamycin (mTOR) that is receiving intense focus as a potential new target for cerebrovascular disease. As part of the phosphoinositide 3-kinase (PI 3-K) and protein kinase B (Akt) cascade, mTOR is an essential component of mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2) to govern cell death involving apoptosis, autophagy, and necroptosis, cellular metabolism, and gene transcription. Vital for the consideration of new therapeutic strategies for stroke is the ability to understand how the intricate and complex pathways of mTOR signaling sometimes lead to disparate clinical outcomes.