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competitive inhibitor of the sirtuins or class III NAD+ dependent HDACs
Development Status:
investigational in U.S.
FDA Phase:
Phase II/IIa/IIb
Primary Medical Role:
Nicotinamide is a water-soluble vitamin that is converted
into niacin in vivo. Niacin is an essential component to
form nicotinamide adenine dinucleotide (NAD) and
nicotinamide adenine dinucleotide phosphate (NADP),
coenzymes involved in redox reactions in all living cells.
Role in Alzheimer's Disease:
In transgenic mouse models of Alzheimer's Disease (Green et
al 2008), nicotinamide has been shown to restore cognition
in water maze tests and improves contextual learning,
preventing fear memory deficits. Nicotinamide did not
reduce plaque deposition or reduce either soluble or
insoluble Ab in 3xTg AD mice, but did decrease tau pathology
and selectively reduced Thr231 phosphorylated tau, known to
inhibit microtubule polymerization. Nicotinamide was also
shown in this study to inhibit sirtuin deacetylase and
increases microtubule stability. Also see Alzforum
News.
Notes:
A Phase I/II clinical trial testing Nicotinamide/Enduramide
(extended-release niacinamide), located at UC Irvine School
of Medicine, is currently recruiting participants. See NCT00580931.
This entry was updated November 16, 2010.
References
Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS,
Thompson LM, LaFerla FM. Nicotinamide restores cognition in
Alzheimer's disease transgenic mice via a mechanism
involving sirtuin inhibition and selective reduction of
Thr231-phosphotau. J Neurosci. 2008 Nov 5;28(45):11500-10. POW Link and Comments