Natural isoprenoids are able to reduce inflammation in a mouse model of mevalonate kinase deficiency.
Mevalonate kinase deficiency (MKD) is a rare disorder characterized by recurrent inflammatory episodes and, in most severe cases, by psychomotor delay. Defective synthesis of isoprenoids has been associated with the inflammatory phenotype in these patients, but the molecular mechanisms involved are still poorly understood, and, so far, no specific therapy is available for this disorder. Drugs like aminobisphosphonates, which inhibit the mevalonate pathway causing a relative defect in isoprenoids synthesis, have been also associated to an inflammatory phenotype. Recent data asserted that cell inflammation could be reversed by the addition of some isoprenoids, such as geranylgeraniol and farnesyl pyrophosphate. In this study, a mouse model for typical MKD inflammatory episode was obtained treating BALB/c mice with aminobisphosphonate alendronate and bacterial muramyldipeptide. The effect of exogenous isoprenoids -- geraniol, farnesol, and geranylgeraniol -- was therefore evaluated in this model. All these compounds were effective in preventing the inflammation induced by alendronate-muramyldipeptide, suggesting a possible role for these compounds in the treatment of MKD in humans.
Marcuzzi
Annalisa
A
Department of Reproductive and Developmental Sciences, University of Trieste, Trieste, Italy.
Pontillo
Alessandra
A
De Leo
Luigina
L
Tommasini
Alberto
A
Decorti
Giuliana
G
Not
Tarcisio
T
Ventura
Alessandro
A
D000119:Acetylmuramyl-Alanyl-Isoglutamine; D000080462:Acyclic Monoterpenes; D019386:Alendronate; D000818:Animals; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology; D005204:Farnesol / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D013729:Terpenes / Q000494:pharmacology / Q000627:therapeutic use*
D000080462:Acyclic Monoterpenes; D004224:Diterpenes; D013729:Terpenes; D005204:Farnesol; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C017338:geranylgeraniol; C007836:geraniol; D019386:Alendronate