The Interaction of mTOR and Nrf2 in Neurogenesis and Its Implication in Neurodegenerative Diseases

Abstract

Neurogenesis occurs in the brain during embryonic development and throughout adulthood. Neurogenesis occurs in the hippocampus and under normal conditions and persists in two regions of the brain-the subgranular zone (SGZ) in the dentate gyrus of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles. As the critical role in neurogenesis, the neural stem cells have the capacity to differentiate into various cells and to self-renew. This process is controlled through different methods. The mammalian target of rapamycin (mTOR) controls cellular growth, cell proliferation, apoptosis, and autophagy. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is a major regulator of metabolism, protein quality control, and antioxidative defense, and is linked to neurogenesis. However, dysregulation in neurogenesis, mTOR, and Nrf2 activity have all been associated with neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's. Understanding the role of these complexes in both neurogenesis and neurodegenerative disease could be necessary to develop future therapies. Here, we review both mTOR and Nrf2 complexes, their crosstalk and role in neurogenesis, and their implication in neurodegenerative diseases.

Keywords: Nrf2; mTOR; neurodegenerative diseases; neurogenesis.

Figure 1

Nrf2 mechanism pathway. Nrf2 is released in the cytoplasm then migrates into the nucleus where it is transcripted during oxidative stress and degraded when it is no longer needed through ubiquitination (see text for more information). The figure was prepared by software provided by Biorender.com (accessed 3 March 2022).

Figure 2

mTOR mechanism pathway. Glucose and growth factors activate a series of pathways that either activate or inhibit (AMPK) mTORC1. Amino acids can either activate mTORC1 or mTORC2, which lead to cytoskeleton organization and cell survival or cell growth and proliferation (see text for more details). The figure was prepared by software provided by Biorender.com (accessed on 3 March 2022).

Figure 3

Nrf2 and mTOR mechanism pathway. AKT is one of the procedures of mTOR activity, which plays an important role in cellular mechanisms such as cell proliferation, cell cycle, and activated p21, which then inhibits Keap1, which alternates the Nrf2 mechanism. The figure was prepared by software provided by Biorender.com (accessed 3 March 2022).