Defining the mechanism of action of 4-phenylbutyrate to develop a small-molecule-based therapy for Alzheimer's disease.

doi:10.2174/092986711798347315

Paper

Defining the mechanism of action of 4-phenylbutyrate to develop a small-molecule-based therapy for Alzheimer's disease.

Published Nov 30, 2011 · M. Cuadrado‐Tejedor, A. García-Osta, A. Ricobaraza

Current medicinal chemistry

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Abstract

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.

Study Snapshot

Deciphering the precise mechanism of action of 4-phenylbutyrate may enable the development of novel, manageable Alzheimer's disease treatments with similar therapeutic effects.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Defining the mechanism of action of 4-phenylbutyrate to develop a small-molecule-based therapy for Alzheimer's disease.

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