RESUMEN

Coenzyme A is an essential metabolite known for its central role in over one hundred cellular metabolic reactions. In cells, Coenzyme A is synthesized de novo in five enzymatic steps with vitamin B5 as the starting metabolite, phosphorylated by pantothenate kinase. Mutations in the pantothenate kinase 2 gene cause a severe form of neurodegeneration for which no treatment is available. One therapeutic strategy is to generate Coenzyme A precursors downstream of the defective step in the pathway. Here we describe the synthesis, characteristics and in vivo rescue potential of the acetyl-Coenzyme A precursor S-acetyl-4'-phosphopantetheine as a possible treatment for neurodegeneration associated with pantothenate kinase deficiency.

Asunto(s)

Trastornos Heredodegenerativos del Sistema Nervioso/tratamiento farmacológico , Panteteína/análogos & derivados , Fosfotransferasas (Aceptor de Grupo Alcohol)/deficiencia , Suero/química , Animales , Línea Celular , Modelos Animales de Enfermedad , Drosophila , Humanos , Ratones , Panteteína/administración & dosificación , Panteteína/síntesis química , Panteteína/aislamiento & purificación , Panteteína/farmacocinética , Resultado del Tratamiento