Metformin is the first-line therapy for diabetes, even in children, and a promising attractive candidate for drug repurposing. Mitochondria are emerging as crucial targets of metformin action both in the periphery and in the brain. The present study evaluated whether treatment with metformin may rescue brain mitochondrial alterations and contrast the increased oxidative stress in a validated mouse model of Rett syndrome (RTT), a rare neurologic disorder of monogenic origin characterized by severe behavioral and physiological symptoms. No cure for RTT is available. In fully symptomatic RTT mice (12 months old MeCP2-308 heterozygous female mice), systemic treatment with metformin (100 mg/kg ip for 10 days) normalized the reduced mitochondrial ATP production and ATP levels in the whole-brain, reduced brain oxidative damage, and rescued the increased production of reactive oxidizing species in blood. A 10-day long treatment with metformin also boosted pathways related to mitochondrial biogenesis and antioxidant defense in the brain of metformin-treated RTT mice. This treatment regimen did not improve general health status and motor dysfunction in RTT mice at an advanced stage of the disease. Present results provide evidence that systemic treatment with metformin may represent a novel, repurposable therapeutic strategy for RTT
The anti-diabetic drug metformin rescues aberrant mitochondrial activity and restrains oxidative stress in a female mouse model of rett syndrome / Zuliani, Ilaria; Urbinati, Chiara; Valenti, Daniela; Cristina Quattrini, Maria; Medici, Vanessa; Cosentino, Livia; Pietraforte, Donatella; DI DOMENICO, Fabio; Perluigi, Marzia; Anna Vacca, Rosa; De Filippis, Bianca. - In: JOURNAL OF CLINICAL MEDICINE. - ISSN 2077-0383. - (2020). [10.3390/jcm9061669]
The anti-diabetic drug metformin rescues aberrant mitochondrial activity and restrains oxidative stress in a female mouse model of rett syndrome
Ilaria ZulianiPrimo
;Chiara Urbinati;Livia Cosentino;Fabio Di Domenico;Marzia Perluigi;
2020
Abstract
Metformin is the first-line therapy for diabetes, even in children, and a promising attractive candidate for drug repurposing. Mitochondria are emerging as crucial targets of metformin action both in the periphery and in the brain. The present study evaluated whether treatment with metformin may rescue brain mitochondrial alterations and contrast the increased oxidative stress in a validated mouse model of Rett syndrome (RTT), a rare neurologic disorder of monogenic origin characterized by severe behavioral and physiological symptoms. No cure for RTT is available. In fully symptomatic RTT mice (12 months old MeCP2-308 heterozygous female mice), systemic treatment with metformin (100 mg/kg ip for 10 days) normalized the reduced mitochondrial ATP production and ATP levels in the whole-brain, reduced brain oxidative damage, and rescued the increased production of reactive oxidizing species in blood. A 10-day long treatment with metformin also boosted pathways related to mitochondrial biogenesis and antioxidant defense in the brain of metformin-treated RTT mice. This treatment regimen did not improve general health status and motor dysfunction in RTT mice at an advanced stage of the disease. Present results provide evidence that systemic treatment with metformin may represent a novel, repurposable therapeutic strategy for RTTFile | Dimensione | Formato | |
---|---|---|---|
Zuliani_The Anti-diabetic_2020.pdf
accesso aperto
Note: https://www.mdpi.com/2077-0383/9/6/1669
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Creative commons
Dimensione
3.82 MB
Formato
Adobe PDF
|
3.82 MB | Adobe PDF |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.