Ascorbic acid (Vitamin C) inhibits PMP22 expression by reducing cAMP levels

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Neuromuscul Disord. 2007 Feb 13

Ascorbic acid inhibits PMP22 expression by reducing cAMP levels.

Kaya F, Sophie B, Bourgeois P, Micaleff J, Blin O, Fontes M.

INSERM UMR491, Centre de Therapie Genique, Genomique et de

Biotherapies (CTGGB), IPHM-IFR125, Faculte de Medecine de la Timone,

27 bd Moulin, 13385 Marseille cedex 5, France.

Charcot-Marie-Tooth [CMT] syndrome is the most common hereditary

peripheral neuropathy. CMT1A, which accounts for 50% of all CMT

cases, usually results from triploidy of the PMP22 gene.

Preclinical trials using an animal model show that disabled mice

force-fed with high doses of ascorbic acid partially recover

muscular strength after a few months of treatment, and suggest that

high doses of ascorbic acid repress PMP22 expression.

In this study, we demonstrated that ascorbic acid represses PMP22

gene expression by acting on intracellular cAMP levels and adenylate

cyclase activity. This action is dose dependent and specific to

ascorbic acid, since repression is not observed after treatment with

other antioxidants. The new properties of ascorbic acid are

discussed, along with the implications of these findings for CMT

disease treatment.