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Biochem Pharmacol. 2014 Apr 15;88(4):605-16. doi: 10.1016/j.bcp.2013.10.030. Epub 2013 Nov 11.

Statins more than cholesterol lowering agents in Alzheimer disease: their pleiotropic functions as potential therapeutic targets.

Author information

1
Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.
2
Department of Biochemical Sciences, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
3
Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA. Electronic address: dabcns@uky.edu.

Abstract

Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairment, inability to perform activities of daily living and mood changes. Statins, long known to be beneficial in conditions where dyslipidemia occurs by lowering serum cholesterol levels, also have been proposed for use in neurodegenerative conditions, including AD. However, it is not clear that the purported effectiveness of statins in neurodegenerative disorders is directly related to cholesterol-lowering effects of these agents; rather, the pleiotropic functions of statins likely play critical roles. The aim of this review is to provide an overview on the new discoveries about the effects of statin therapy on the oxidative and nitrosative stress levels as well as on the modulation of the heme oxygenase/biliverdin reductase (HO/BVR) system in the brain. We propose a novel mechanism of action for atorvastatin which, through the activation of HO/BVR-A system, may contribute to the neuroprotective effects thus suggesting a potential therapeutic role in AD and potentially accounting for the observation of decreased AD incidence with persons on statin.

KEYWORDS:

Alzheimer disease; Biliverdin reductase; Cognition; Heme oxygenase; Oxidative stress; Statin

PMID:
24231510
PMCID:
PMC3972306
DOI:
10.1016/j.bcp.2013.10.030
[Indexed for MEDLINE]
Free PMC Article

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