» Articles » PMID: 32120979

Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders?

Overview
Journal Molecules
Publisher MDPI
Specialty Biology
Date 2020 Mar 4
PMID 32120979
Citations 24
Authors
Affiliations
Soon will be listed here.
Abstract

Recently, peroxisome proliferator-activated receptor (PPAR)-α and γ isoforms have been gaining consistent interest in neuropathology and treatment of neuropsychiatric disorders. Several studies have provided evidence that either the receptor expression or the levels of their endogenously-produced modulators are downregulated in several neurological and psychiatric disorders and in their respective animal models. Remarkably, administration of these endogenous or synthetic ligands improves mood and cognition, suggesting that PPARs may offer a significant pharmacological target to improve several neuropathologies. Furthermore, various neurological and psychiatric disorders reflect sustained levels of systemic inflammation. Hence, the strategy of targeting PPARs for their anti-inflammatory role to improve these disorders is attracting attention. Traditionally, classical antidepressants fail to be effective, specifically in patients with inflammation. Non-steroidal anti-inflammatory drugs exert potent antidepressant effects by acting along with PPARs, thereby strongly substantiating the involvement of these receptors in the mechanisms that lead to development of several neuropathologies. We reviewed running findings in support of a role for PPARs in the treatment of neurological diseases, including Alzheimer's disease or psychiatric disorders, such as major depression. We discuss the opportunity of targeting PPARs as a future pharmacological approach to decrease neuropsychiatric symptoms at the same time that PPAR ligands resolve neuroinflammatory processes.

Citing Articles

Progesterone Promotes Anti-Anxiety/Depressant-like Behavior and Trophic Actions of BDNF in the Hippocampus of Female Nuclear Progesterone Receptor, but Not 5α-Reductase, Knockout Mice.

Frye C, Cleveland D, Sadarangani A, Torgersen J Int J Mol Sci. 2025; 26(3).

PMID: 39940941 PMC: 11818940. DOI: 10.3390/ijms26031173.


Body and mind: how obesity triggers neuropsychiatric and neurodegenerative disorders.

Pirozzi C, Opallo N, Del Piano F, Melini S, Lama A Front Psychiatry. 2025; 15():1524555.

PMID: 39839130 PMC: 11747159. DOI: 10.3389/fpsyt.2024.1524555.


Perindopril Ameliorates Sodium Valproate-Induced Rat Model of Autism: Involvement of Sirtuin-1, JAK2/STAT3 Axis, PI3K/Akt/GSK-3β Pathway, and PPAR-Gamma Signaling.

Alnakhli A, Saleh A, Kabel A, Estfanous R, Borg H, Alsufyani K Medicina (Kaunas). 2024; 60(11).

PMID: 39596986 PMC: 11596946. DOI: 10.3390/medicina60111802.


The Alpha-7 Nicotinic Receptor Positive Allosteric Modulator PNU120596 Attenuates Lipopolysaccharide-Induced Depressive-Like Behaviors and Cognitive Impairment by Regulating the PPAR-α Signaling Pathway in Mice.

Alzarea S, Rahman S CNS Neurol Disord Drug Targets. 2024; 24(3):234-244.

PMID: 39350553 DOI: 10.2174/0118715273311527240916050749.


PPARβ/δ Agonist GW0742 Modulates Microglial and Astroglial Gene Expression in a Rat Model of Temporal Lobe Epilepsy.

Zubareva O, Kharisova A, Roginskaya A, Kovalenko A, Zakharova M, Schwarz A Int J Mol Sci. 2024; 25(18).

PMID: 39337503 PMC: 11432388. DOI: 10.3390/ijms251810015.


References
1.
Albert P, Benkelfat C, Descarries L . The neurobiology of depression--revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms. Philos Trans R Soc Lond B Biol Sci. 2012; 367(1601):2378-81. PMC: 3405681. DOI: 10.1098/rstb.2012.0190. View

2.
Agis-Balboa R, Pinna G, Pibiri F, Kadriu B, Costa E, Guidotti A . Down-regulation of neurosteroid biosynthesis in corticolimbic circuits mediates social isolation-induced behavior in mice. Proc Natl Acad Sci U S A. 2007; 104(47):18736-41. PMC: 2141846. DOI: 10.1073/pnas.0709419104. View

3.
Capano L, Dupuis A, Brian J, Mankad D, Genore L, Adams R . A pilot dose finding study of pioglitazone in autistic children. Mol Autism. 2018; 9:59. PMC: 6258310. DOI: 10.1186/s13229-018-0241-5. View

4.
Rasmusson A, Pinna G, Paliwal P, Weisman D, Gottschalk C, Charney D . Decreased cerebrospinal fluid allopregnanolone levels in women with posttraumatic stress disorder. Biol Psychiatry. 2006; 60(7):704-13. DOI: 10.1016/j.biopsych.2006.03.026. View

5.
Klotz L, Schmidt S, Heun R, Klockgether T, Kolsch H . Association of the PPARgamma gene polymorphism Pro12Ala with delayed onset of multiple sclerosis. Neurosci Lett. 2008; 449(1):81-3. DOI: 10.1016/j.neulet.2008.10.066. View