PPARα Signaling: A Candidate Target in Psychiatric Disorder Management
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,...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/12/5/723 |
| _version_ | 1797501234819629056 |
|---|---|
| author | Simona Scheggi Graziano Pinna Giulia Braccagni Maria Graziella De Montis Carla Gambarana |
| author_facet | Simona Scheggi Graziano Pinna Giulia Braccagni Maria Graziella De Montis Carla Gambarana |
| author_sort | Simona Scheggi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T03:15:28Z |
| format | Article |
| id | doaj.art-4f45694635de43fc882f100b6043c7c3 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T03:15:28Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-4f45694635de43fc882f100b6043c7c32023-11-23T10:14:39ZengMDPI AGBiomolecules2218-273X2022-05-0112572310.3390/biom12050723PPARα Signaling: A Candidate Target in Psychiatric Disorder ManagementSimona Scheggi0Graziano Pinna1Giulia Braccagni2Maria Graziella De Montis3Carla Gambarana4Department of Molecular and Developmental Medicine, University of Siena, Via Aldo Moro 2, 53100 Siena, ItalyDepartment of Psychiatry, The Psychiatric Institute, University of Illinois Chicago, Chicago, IL 60607, USADepartment of Molecular and Developmental Medicine, University of Siena, Via Aldo Moro 2, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, Via Aldo Moro 2, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, Via Aldo Moro 2, 53100 Siena, ItalyPeroxisome 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.https://www.mdpi.com/2218-273X/12/5/723N-acylethanolaminesendocannabinoidsneurosteroidsfenofibratedopamineneuroinflammation |
| spellingShingle | Simona Scheggi Graziano Pinna Giulia Braccagni Maria Graziella De Montis Carla Gambarana PPARα Signaling: A Candidate Target in Psychiatric Disorder Management Biomolecules N-acylethanolamines endocannabinoids neurosteroids fenofibrate dopamine neuroinflammation |
| title | PPARα Signaling: A Candidate Target in Psychiatric Disorder Management |
| title_full | PPARα Signaling: A Candidate Target in Psychiatric Disorder Management |
| title_fullStr | PPARα Signaling: A Candidate Target in Psychiatric Disorder Management |
| title_full_unstemmed | PPARα Signaling: A Candidate Target in Psychiatric Disorder Management |
| title_short | PPARα Signaling: A Candidate Target in Psychiatric Disorder Management |
| title_sort | pparα signaling a candidate target in psychiatric disorder management |
| topic | N-acylethanolamines endocannabinoids neurosteroids fenofibrate dopamine neuroinflammation |
| url | https://www.mdpi.com/2218-273X/12/5/723 |
| work_keys_str_mv | AT simonascheggi pparasignalingacandidatetargetinpsychiatricdisordermanagement AT grazianopinna pparasignalingacandidatetargetinpsychiatricdisordermanagement AT giuliabraccagni pparasignalingacandidatetargetinpsychiatricdisordermanagement AT mariagraziellademontis pparasignalingacandidatetargetinpsychiatricdisordermanagement AT carlagambarana pparasignalingacandidatetargetinpsychiatricdisordermanagement |