The neuropsychopharmacology of acetyl-L-carnitine (LAC): basic, translational and therapeutic implications.
Cognition
Depression
Glutamate
Hippocampus
Histone acetylation
Journal
Discover mental health
ISSN: 2731-4383
Titre abrégé: Discov Ment Health
Pays: Switzerland
ID NLM: 9918350483906676
Informations de publication
Date de publication:
02 Jan 2024
02 Jan 2024
Historique:
received:
21
08
2023
accepted:
15
12
2023
medline:
4
1
2024
pubmed:
4
1
2024
entrez:
3
1
2024
Statut:
epublish
Résumé
Mitochondrial metabolism can contribute to nuclear histone acetylation among other epigenetic mechanisms. A central aspect of this signaling pathway is acetyl-L-carnitine (LAC), a pivotal mitochondrial metabolite best known for its role in fatty acid oxidation. Work from our and other groups suggested LAC as a novel epigenetic modulator of brain plasticity and a therapeutic target for clinical phenotypes of depression linked to childhood trauma. Aberrant mitochondrial metabolism of LAC has also been implicated in the pathophysiology of Alzheimer's disease. Furthermore, mitochondrial dysfunction is linked to other processes implicated in the pathophysiology of both major depressive disorders and Alzheimer's disease, such as oxidative stress, inflammation, and insulin resistance. In addition to the rapid epigenetic modulation of glutamatergic function, preclinical studies showed that boosting mitochondrial metabolism of LAC protects against oxidative stress, rapidly ameliorates insulin resistance, and reduces neuroinflammation by decreasing proinflammatory pathways such as NFkB in hippocampal and cortical neurons. These basic and translational neuroscience findings point to this mitochondrial signaling pathway as a potential target to identify novel mechanisms of brain plasticity and potential unique targets for therapeutic intervention targeted to specific clinical phenotypes.
Identifiants
pubmed: 38169018
doi: 10.1007/s44192-023-00056-z
pii: 10.1007/s44192-023-00056-z
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
2Subventions
Organisme : NIH HHS
ID : R01MH128311
Pays : United States
Informations de copyright
© 2023. The Author(s).
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