Puighermanal 2024 Nat Commun
| Puighermanal E, Luna-SΓ‘nchez M, Gella A, van der Walt G, Urpi A, Royo M, Tena-Morraja P, Appiah I, de Donato MH, Menardy F, Bianchi P, Esteve-Codina A, RodrΓguez-Pascau L, Vergara C, GΓ³mez-PallarΓ¨s M, Marsicano G, Bellocchio L, Martinell M, Sanz E, Jurado S, Soriano FX, Pizcueta P, Quintana A (2024) Cannabidiol ameliorates mitochondrial disease via PPARΞ³ activation in preclinical models. Nat Commun 15:7730. https://doi.org/10.1038/s41467-024-51884-8 |
Puighermanal Emma, Luna-Sanchez Marta, Gella Alejandro, van der Walt Gunter, Urpi Andrea, Royo Maria, Tena-Morraja Paula, Appiah Isabella, de Donato Maria Helena, Menardy Fabien, Bianchi Patrizia, Esteve-Codina Anna, Rodriguez-Pascau Laura, Vergara Cristina, Gomez-Pallares Merce, Marsicano Giovanni, Bellocchio Luigi, Martinell Marc, Sanz Elisenda, Jurado Sandra, Soriano Francesc Xavier, Pizcueta Pilar, Quintana Albert (2024) Nat Commun
Abstract: Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and improves cellular function in fibroblasts from LS patients. CBD delays motor decline and neurodegenerative signs, improves social deficits and breathing abnormalities, decreases thermally induced seizures, and improves neuropathology in affected brain regions. Mechanistically, we identify peroxisome proliferator-activated receptor gamma (PPARΞ³) as a key nuclear receptor mediating CBD's beneficial effects, while also providing proof of dysregulated PPARΞ³ expression and activity as a common feature in both mouse neurons and fibroblasts from LS patients. Taken together, our results provide the first evidence for CBD as a potential treatment for LS.
β’ Bioblast editor: Plangger M
Labels: MiParea: Respiration, Genetic knockout;overexpression, Pharmacology;toxicology
Stress:Mitochondrial disease Organism: Mouse Tissue;cell: Nervous system Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS
Pathway: N, S
HRR: Oxygraph-2k
2024-09
