Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (4): 1552-1553.doi: 10.4103/NRR.NRR-D-24-00961

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mTORC1 and mTORC2 synergy in human neural development, disease, and regeneration

Navroop K. Dhaliwal, Julien Muffat, Yun Li*   

  1. Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada (Muffat J) Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada (Dhaliwal NK, Li Y) Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada (Muffat J, Li Y)
  • Online:2026-04-15 Published:2025-07-27
  • Contact: Yun Li, PhD, yun.li@sickkids.ca.
  • Supported by:
    We thank all members of the Li and Muffat Labs for helpful discussions. This work was supported by grants from Simons Foundation (SFARI 479754), CIHR (PJT-180565), and the Scottish Rite Charitable Foundation of Canada (to YL). JM received funding from the Canada Research Chairs program.

Abstract: The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system (CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the mTOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies” (Crino, 2020). Dysfunctions of mTOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health. Molecularly, mTOR functions as the catalytic subunit of two distinct complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). These two complexes are defined by their unique components and substrate specificities, which in turn activate distinct downstream signaling cascades that underpin their diverse roles in the CNS. mTORC1, characterized by the presence of RPTOR (Regulatory Associated Protein of MTOR complex 1), is known to govern protein synthesis and autophagy. In contrast, mTORC2, which contains RICTOR (RPTOR Independent Companion of MTOR complex 2), is less understood but is known to regulate the actin cytoskeleton and metabolism.