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Biomolecules
Special Issues
Role of PPARs in Neurological and Psychiatric Disorders
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Role of PPARs in Neurological and Psychiatric Disorders

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Nucleic Acids".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 8492

Special Issue Editor

Dr. Maria Graziella De Montis

E-Mail Website
Guest Editor
Pharmacology Unit, Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy
Interests: PPAR ligands; CNS disorders; neuroinflammation; mitochondrial disfunction

Special Issue Information

Dear Colleagues,

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate gene expression by binding to specific peroxisome proliferator response elements on responsive genes. Three isoforms of PPARs have been identified (PPAR-α, PPAR-γ, and PPAR-β/δ), all of which are involved in an array of molecular steps that regulate metabolism and inflammation. Recently, evidence of the roles that PPARs play in central nervous system (CNS) functions has emerged. Preclinical studies, performed on experimental models of different neurological/neurodegenerative, neurodevelopmental, and psychiatric disorders, and a limited number of clinical studies suggest that PPARs may represent promising therapeutic targets for CNS diseases. For disorders such as Alzheimer’s disease, Parkinson’s disease, epilepsy, and autism spectrum disorders, but also for major depression and substance abuse, the available therapeutic tools are often still unsatisfactory, and there is an urgent need for advances in neuropsychopharmacology research that usher in the development of novel therapeutic strategies.

This Special Issue of Biomolecules is dedicated to PPAR and their endogenous and synthetic ligands, with the goal of providing an up-to-date view of the role of the PPAR system in the pathophysiology and treatment of psychiatric, developmental, and neurodegenerative disorders that may lead to the identification and development of effective novel therapeutic agents. Colleagues from different fields are invited to submit original research articles, reviews, or perspective articles on all aspects related to the involvement of the PPAR system in the healthy and diseased brain.

Dr. Maria Graziella De Montis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • PPAR ligands
  • CNS disorders
  • neuroinflammation
  • mitochondrial disfunction

Published Papers (2 papers)

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Review

20 pages, 2502 KiB  
Review
PPARα Signaling: A Candidate Target in Psychiatric Disorder Management
by Simona Scheggi, Graziano Pinna, Giulia Braccagni, Maria Graziella De Montis and Carla Gambarana
Biomolecules 2022, 12(5), 723; https://doi.org/10.3390/biom12050723 - 20 May 2022
Cited by 7 | Viewed by 3614
Abstract
Peroxisome proliferator-activator receptors (PPARs) regulate lipid and glucose metabolism, control inflammatory processes, and modulate several brain functions. Three PPAR isoforms have been identified, PPARα, PPARβ/δ, and PPARγ, which are expressed in different tissues and cell types. Hereinafter, we focus on PPARα involvement in [...] Read more.
Peroxisome proliferator-activator receptors (PPARs) regulate lipid and glucose metabolism, control inflammatory processes, and modulate several brain functions. Three PPAR isoforms have been identified, PPARα, PPARβ/δ, and PPARγ, which are expressed in different tissues and cell types. Hereinafter, we focus on PPARα involvement in the pathophysiology of neuropsychiatric and neurodegenerative disorders, which is underscored by PPARα localization in neuronal circuits involved in emotion modulation and stress response, and its role in neurodevelopment and neuroinflammation. A multiplicity of downstream pathways modulated by PPARα activation, including glutamatergic neurotransmission, upregulation of brain-derived neurotrophic factor, and neurosteroidogenic effects, encompass mechanisms underlying behavioral regulation. Modulation of dopamine neuronal firing in the ventral tegmental area likely contributes to PPARα effects in depression, anhedonia, and autism spectrum disorder (ASD). Based on robust preclinical evidence and the initial results of clinical studies, future clinical trials should assess the efficacy of PPARα agonists in the treatment of mood and neurodevelopmental disorders, such as depression, schizophrenia, and ASD. Full article
(This article belongs to the Special Issue Role of PPARs in Neurological and Psychiatric Disorders)
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13 pages, 1791 KiB  
Review
Repurposing Small Molecules to Target PPAR-γ as New Therapies for Peripheral Nerve Injuries
by Melissa L. D. Rayner, Jess Healy and James B. Phillips
Biomolecules 2021, 11(9), 1301; https://doi.org/10.3390/biom11091301 - 01 Sep 2021
Cited by 10 | Viewed by 4219
Abstract
The slow rate of neuronal regeneration that follows peripheral nerve repair results in poor recovery, particularly where reinnervation of muscles is delayed, leading to atrophy and permanent loss of function. There is a clear clinical need to develop drug treatments that can accelerate [...] Read more.
The slow rate of neuronal regeneration that follows peripheral nerve repair results in poor recovery, particularly where reinnervation of muscles is delayed, leading to atrophy and permanent loss of function. There is a clear clinical need to develop drug treatments that can accelerate nerve regeneration safely, restoring connections before the target tissues deteriorate irreversibly. The identification that the Rho/Rho-associated kinase (ROCK) pathway acts to limit neuronal growth rate is a promising advancement towards the development of drugs. Targeting Rho or ROCK directly can act to suppress the activity of this pathway; however, the pathway can also be modulated through the activation of upstream receptors; one of particular interest being peroxisome proliferator-activated receptor gamma (PPAR-γ). The connection between the PPAR-γ receptor and the Rho/ROCK pathway is the suppression of the conversion of inactive guanosine diphosphate (GDP)-Rho to active guanosine triphosphate GTP-Rho, resulting in the suppression of Rho/ROCK activity. PPAR-γ is known for its role in cellular metabolism that leads to cell growth and differentiation. However, more recently there has been a growing interest in targeting PPAR-γ in peripheral nerve injury (PNI). The localisation and expression of PPAR-γ in neural cells following a PNI has been reported and further in vitro and in vivo studies have shown that delivering PPAR-γ agonists following injury promotes nerve regeneration, leading to improvements in functional recovery. This review explores the potential of repurposing PPAR-γ agonists to treat PNI and their prospective translation to the clinic. Full article
(This article belongs to the Special Issue Role of PPARs in Neurological and Psychiatric Disorders)
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