Recent Insights into Toll-Like Receptors and Their Role in Psychiatric Disorders

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (1 June 2023) | Viewed by 3295

Special Issue Editor

Pharmacology & Therapeutics, National University of Ireland, H91 W5P7 Galway, Ireland
Interests: neuroinflammation; pattern recognition receptors; schizophrenia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Toll-like receptors (TLRs) are a key component of the innate immune system. They are pattern recognition receptors that are responsible for initiating the inflammatory response following microbial infection but also as a result of tissue damage and stress. TLRs were initially associated with chronic inflammatory diseases, but in recent years, there has been a growing interest in their potential role in psychiatric disorders such as schizophrenia, bipolar disorder, and depression. GWAS studies have reported genetic associations with the innate immune system, animal models have used TLR agonists to mimic behavioral phenotypes, and alterations in peripheral TLR activity have been reported in psychiatric populations. This Special Issue seeks to understand the role of these proteins in psychiatric disorders and how they might be targeted in the treatment of such disorders. Original manuscripts and reviews dealing with any aspect of synucleins and related pathophysiology are very welcome.

Dr. Declan McKernan
Guest Editor

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Keywords

  • Toll-like receptors
  • inflammation
  • neuroinflammation
  • psychiatric disorders

Published Papers (2 papers)

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Review

16 pages, 1460 KiB  
Review
The Role of the Adrenal–Gut–Brain Axis on Comorbid Depressive Disorder Development in Diabetes
by Thalita Mázala-de-Oliveira, Bruna Teixeira Silva, Paula Campello-Costa and Vinicius Frias Carvalho
Biomolecules 2023, 13(10), 1504; https://doi.org/10.3390/biom13101504 - 10 Oct 2023
Cited by 2 | Viewed by 1547
Abstract
Diabetic patients are more affected by depression than non-diabetics, and this is related to greater treatment resistance and associated with poorer outcomes. This increase in the prevalence of depression in diabetics is also related to hyperglycemia and hypercortisolism. In diabetics, the hyperactivity of [...] Read more.
Diabetic patients are more affected by depression than non-diabetics, and this is related to greater treatment resistance and associated with poorer outcomes. This increase in the prevalence of depression in diabetics is also related to hyperglycemia and hypercortisolism. In diabetics, the hyperactivity of the HPA axis occurs in parallel to gut dysbiosis, weakness of the intestinal permeability barrier, and high bacterial-product translocation into the bloodstream. Diabetes also induces an increase in the permeability of the blood–brain barrier (BBB) and Toll-like receptor 4 (TLR4) expression in the hippocampus. Furthermore, lipopolysaccharide (LPS)-induced depression behaviors and neuroinflammation are exacerbated in diabetic mice. In this context, we propose here that hypercortisolism, in association with gut dysbiosis, leads to an exacerbation of hippocampal neuroinflammation, glutamatergic transmission, and neuronal apoptosis, leading to the development and aggravation of depression and to resistance to treatment of this mood disorder in diabetic patients. Full article
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22 pages, 3149 KiB  
Review
Counting the Toll of Inflammation on Schizophrenia—A Potential Role for Toll-like Receptors
by Saahithh Redddi Patlola, Gary Donohoe and Declan P. McKernan
Biomolecules 2023, 13(8), 1188; https://doi.org/10.3390/biom13081188 - 30 Jul 2023
Cited by 1 | Viewed by 1283
Abstract
Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that are ubiquitously expressed in the human body. They protect the brain and central nervous system from self and foreign antigens/pathogens. The immune response elicited by these receptors culminates in the release [...] Read more.
Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that are ubiquitously expressed in the human body. They protect the brain and central nervous system from self and foreign antigens/pathogens. The immune response elicited by these receptors culminates in the release of cytokines, chemokines, and interferons causing an inflammatory response, which can be both beneficial and harmful to neurodevelopment. In addition, the detrimental effects of TLR activation have been implicated in multiple neurodegenerative diseases such as Alzheimer’s, multiple sclerosis, etc. Many studies also support the theory that cytokine imbalance may be involved in schizophrenia, and a vast amount of literature showcases the deleterious effects of this imbalance on cognitive performance in the human population. In this review, we examine the current literature on TLRs, their potential role in the pathogenesis of schizophrenia, factors affecting TLR activity that contribute towards the risk of schizophrenia, and lastly, the role of TLRs and their impact on cognitive performance in schizophrenia. Full article
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