Therapeutic modulation of JAK-STAT, mTOR, and PPAR-γ signaling in neurological dysfunctions

The cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) cascade is a pleiotropic pathway that involves receptor subunit multimerization. The mammalian target of rapamycin (mTOR) is a ubiquitously expressed serine-threonine kinase that perceives and integrates a variety of intracellular and environmental stimuli to regulate essential activities such as cell development and metabolism. Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a prototypical metabolic nuclear receptor involved in neural differentiation and axon polarity. The JAK-STAT, mTOR, and PPAR gamma signaling pathways serve as a highly conserved signaling hub that coordinates neuronal activity and brain development. Additionally, overactivation of JAK/STAT, mTOR, and inhibition of PPAR gamma signaling have been linked to various neurocomplications, including neuroinflammation, apoptosis, and oxidative stress. Emerging research suggests that even minor disruptions in these cellular and molecular processes can have significant consequences manifested as neurological and neuropsychiatric diseases. Of interest, target modulators have been proven to alleviate neuronal complications associated with acute and chronic neurological deficits. This research-based review explores the therapeutic role of JAK-STAT, mTOR, and PPAR gamma signaling modulators in preventing neuronal dysfunctions in preclinical and clinical investigations.

Automated summary

The JAK-STAT, mTOR, and PPAR gamma signaling pathways play important roles in neuronal activity and brain development, and their overactivation or inhibition can lead to neurocomplications. Even minor disruptions in cellular and molecular processes can have significant consequences as neurological and neuropsychiatric diseases. Therefore, modulators of these signaling pathways may serve as potential therapeutic targets for preventing neuronal dysfunctions.