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Defining the mechanism of action of 4-phenylbutyrate to develop a small-molecule-based therapy for Alzheimer's disease.
Autor(es) : Cuadrado-Tejedor, M. (Mar)
Garcia-Osta, A. (Ana)
Ricobaraza, A. (Ana)
Oyarzabal, J. (J.)
Franco, R. (Rafael)
Palabras clave : Alzheimer's disease
chaperone
histone deacetylase
phenylbutyrate
amyloid and Tau
amyloid
Tau
4-phenylbutyrate
multi-target mechanism
enzymes
therapeutic effects
Fecha incorporación: 2011
Editorial : Bentham Science Publ LTD
ISSN: 0929-8673
Cita: Cuadrado-Tejedor M, Garcia-Osta A, Ricobaraza A, Oyarzabal J, Franco R. Defining the mechanism of action of 4-phenylbutyrate to develop a small-molecule-based therapy for Alzheimer's disease. Curr Med Chem 2011;18(36):5545-5553.
Resumen
4-phenylbutyrate (PBA) is a small molecule that restores cognitive deficits in animal models of Alzheimer's disease (AD). Although the molecular basis of the cognitive benefits of PBA remains unknown, a multi-modal/multi-target mechanism has been proposed. Putative targets of this drug are different from those of drugs that are now used in clinical trials. As PBA is already administered to patients with congenital defects affecting enzymes in the urea cycle, it can be rapidly tested in AD clinical trials. However, the main drawback to its therapeutic use is the high dosage required (up to 15 g/day). Thus, deciphering the precise mechanism(s) of action of this drug may enable novel drugs with similar therapeutic effects to PBA to be developed that can be used at more manageable doses.
Enlace permanente: http://hdl.handle.net/10171/23299
Aparece en las colecciones: DA - Medicina - Anatomía - Artículos de revista

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