期刊
CURRENT MEDICINAL CHEMISTRY
卷 18, 期 36, 页码 5545-5553出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986711798347315
关键词
Alzheimer's disease; chaperone; histone deacetylase; phenylbutyrate; amyloid and Tau
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.
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