TLR/mTOR inflammatory signaling pathway: novel insight for the treatment of schizophrenia

Author:

Lashgari Naser-Aldin12ORCID,Roudsari Nazanin Momeni12ORCID,Shamsnia Hedieh Sadat12ORCID,Shayan Maryam34ORCID,Momtaz Saeideh56ORCID,Abdolghaffari Amir Hossein12ORCID

Affiliation:

1. Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

2. GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran

3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

4. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

5. Medicinal Plants Research Center, Institute of Medicinal Plants, The Academic Center for Education, Culture and Research (ACECR), Karaj, Iran

6. Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), and Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Abstract

The Toll-like receptor (TLR)/mammalian target of rapamycin (mTOR) signaling pathway is involved in the intracellular regulation of protein synthesis, specifically the ones that mediate neuronal morphology and facilitate synaptic plasticity. The activity of TLR/mTOR signaling has been disrupted, leading to neurodevelopment and deficient synaptic plasticity, which are the main symptoms of schizophrenia. The TLR receptor activates the mTOR signaling pathway and increases the elevation of inflammatory cytokines. Interleukin (IL)-6 is the most commonly altered cytokine, while IL-1, tumor necrosis factor, and interferon (IFN) also lead to SCZ. Anti-inflammatory and anti-oxidative agents such as celecoxib, aspirin, minocycline, and omega-3 fatty acids have shown efficiency against SCZ. As a result, inhibition of the inflammatory process could be suggested for the treatment of SCZ. So mTOR/TLR blockers represent the treatment of SCZ due to their inflammatory consequences. The objective of the present work was to find a novel anti-inflammatory agent that may block the mTOR/TLR inflammatory signaling pathways and might pave the way for the treatment of neuroinflammatory SCZ. Data were collected from experimental and clinical studies published in English between 1998 and October 2022 from Google Scholar, PubMed, Scopus, and the Cochrane library.

Publisher

Canadian Science Publishing

Subject

Physiology (medical),Pharmacology,General Medicine,Physiology

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