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 Zuliani
Primo
;
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 RTT
2020
mecp2; rett syndrome; metformin; nrf2; pgc-1α
01 Pubblicazione su rivista::01a Articolo in rivista
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]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1406139
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