Targeting the mTOR Pathway with Natural Products: A Potential Therapeutic Approach for Autism Spectrum Disorders.

Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by a diverse range of challenges and strengths in social communication, behavior, and sensory processing, with wide variation in presentation and severity among individuals. Treatment for ASD symptoms typically includes stimulants, modafinil, atomoxetine, antidepressants, antipsychotics, and natural products. The mechanistic target of rapamycin (mTOR), a serine/threonine kinase, is dysregulated in many human diseases, leading to abnormal synapse formation, neuroinflammation, and mitochondrial dysfunction. Natural products, due to their wide range of bioactive compounds and relatively low toxicity, have emerged as promising modulators of this pathway. Several phytochemicals-including curcumin, resveratrol, and epigallocatechin gallate-have demonstrated the ability to modulate mTOR signaling and improve neurobehavioral outcomes in preclinical models of ASD. mTORC1 and mTORC2 are key regulators of cellular processes, with mTORC1 being largely sensitive to nutrient availability and mTORC2 playing a crucial role in cell growth, proliferation, motility, and autophagy, which is modulated by the PI3K/Akt/mTOR pathway. Future research should examine the relationship between autism and the mTOR signaling pathway, as well as the phytochemicals that may contribute to improving the condition through this pathway.