Atorvastatin treatment in a dog preclinical model of Alzheimer's disease leads to up-regulation of haem oxygenase-1 and is associated with reduced oxidative stress in brain

Cesare Mancuso, Eugenio Barone, Da Butterfield, F Di Domenico, G Cenini, R Sultana, Mp Murphy, E Head

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Only acetylcholinesterase inhibitors and the NMDA antagonist memantine are approved for AD treatment. Recent preclinical and epidemiological studies proposed statins as novel therapeutics for AD, but the mechanisms of action are still unknown. Here, we demonstrate that atorvastatin (80 mg/d for 14.5 months) treatment resulted in an up-regulation of the inducible isoform of haem oxygenase (HO-1), an enzyme with significant neuroprotective activity. Atorvastatin selectively increased HO-1 in the parietal cortex but not cerebellum. In contrast, HO-2 was increased in cerebellum but not parietal cortex. No changes were observed in HO-1 or HO-2 in the liver. Significant negative correlations between HO-1 and oxidative stress indices and positive correlations with glutathione levels in parietal cortex were found. HO-1 up-regulation significantly correlated with lower discrimination learning error scores in aged beagles. Reference to therapeutic applications of atorvastatin in AD is discussed.
Lingua originaleEnglish
pagine (da-a)981-987
Numero di pagine7
RivistaInternational Journal of Neuropsychopharmacology
Volume15
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • Atorvastatin
  • Heme Oxygenase-1

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