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

Eugenio Barone, Fabio Di Domenico, D. Allan Butterfield

Research output: Contribution to journalReview articlepeer-review

84 Scopus citations

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.

Original languageEnglish
Pages (from-to)605-616
Number of pages12
JournalBiochemical Pharmacology
Volume88
Issue number4
DOIs
StatePublished - Apr 15 2014

Bibliographical note

Funding Information:
This work was supported in part by an NIH grant to DAB [ AG-05119 ].

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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