Rheb + NR1

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mTORC1 signaling influences numerous cellular processes, including protein synthesis and degradation, nucleotide synthesis, cell proliferation, and autophagy. Aberrant mTORC1 signaling, however, is associated with neurodegenerative diseases, cancers, and disorders. Consequently, a need exists for selective inhibition of mTORC1 that can be used to treat chronic diseases without the adverse effects of downregulating or inhibiting mTORC2. Signaling of mTORC1 is regulated by the heterotrimeric TSC complex. The sequence of events when the TSC complex is disrupted unfolds as follows: TSC1/TSC2 (GAP) are inactivated due to phosphorylation on specific amino acids –> GAP becomes non-functional –> consequently, GAP cannot hydrolyze GTP on the Rheb G protein –> Rheb-GTP can then activate mTORC1. Rheb binds to mTORC1 in the Switch II region, activating mTORC1. Given Rheb's selective role in mTORC1, which has no direct impact on mTORC2, targeting Rheb with a suitable molecular inhibitor is a viable option for blocking activity and treating chronic diseases effectively.