LARS2 Activators

LARS2 Activators enhance the function of the leucyl-tRNA synthetase 2 (LARS2) enzyme through various biochemical pathways. Lithium chloride, for example, protects LARS2 from degradation by inhibiting GSK-3, which is known to phosphorylate and target proteins for degradation. This increases the stability and availability of LARS2 for its role in aminoacyl-tRNA synthesis. Similarly, metformin activates AMPK, which then enhances the energy sensing and metabolic regulation functions of LARS2, a response crucial for the proper synthesis of proteins in response to cellular energy states.

Salubrinal's inhibition of eIF2α dephosphorylation indirectly enhances the stress response pathways involving LARS2, thereby promoting its functional activity under stress conditions. Resveratrol, through SIRT1 activation, improves mitochondrial function and biogenesis, processes that are essential for the proper functioning of LARS2. On the other hand, AICAR and Phenformin, both AMPK agonists, enhance the role of LARS2 by mimicking cellular energy depletion and increasing the cellular energy charge, respectively. AMPK activation leads to a metabolic upregulationwhere LARS2 is required for the proper sensing and response to energy states and amino acid availability. Rapamycin and Torin 1, as mTOR inhibitors, upregulate LARS2 by reducing the activity of a pathway that is involved in the regulation of protein synthesis and cell growth, both of which necessitate LARS2's enzymatic activity for linking amino acids to their corresponding tRNA molecules. The inhibition of mTOR can lead to a cellular environment that supports the upregulation of aminoacyl-tRNA synthetases as a compensatory mechanism to maintain protein synthesis.PF-4708671's inhibition of S6K1 disrupts a downstream component of the mTOR pathway, leading to similar upregulatory effects on LARS2 as those seen with mTOR inhibitors. Phenformin's effect, like metformin's, is via AMPK activation, which again ties back to the regulation of energy metabolism and the maintenance of protein synthesis under conditions of metabolic stress.