FoxO3a overexpression prevents both glycogen overload and autophagic buildup in Pompe disease

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Pichon, Julien | Lagalice, Lydie | Deniaud, Johan | Babarit, Candice | Maurier, Virginie | Dubreil, Laurence | Larcher, Thibaut | Ayuso, Eduard | Ciron, Carine | Rouger, Karl | Colle, Marie-Anne

Edité par CCSD -

Pompe disease (glycogen storage disease type II) is a lysosomal storage disorder caused by the mutation of acid α-glucosidase (Gaa), the unique enzyme degrading glycogen in glucose into lysosomes. A massive glycogen overload is described in Pompe patients, mainly in skeletal and cardiac muscles. Furthermore, severe impairment of autophagic flux has been described, highlighted by autophagic buildup. Contrary to cardiac muscle, no treatment currently allows to cure efficiently and durably the skeletal muscle. We have identified the transcription factor Forkhead box O3 (FoxO3a) as a potential target to alleviate skeletal muscle impairments through its key role on regulation of both glycogen homeostasis and autophagy.The objectives of the study were:1/ to explore the preventive effect of FoxO3a overexpression on :- glycogen overload- autophagic flux impairments2/ to investigate the impact of FoxO3a overexpression on skeletal muscle remodeling

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