title: Cholesterol-independent neuroprotective and neurotoxic activities of statins: perspectives for statin use in Alzheimer disease and other age-related neurodegenerative disorders.
abstract: 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 Alzheimer disease. 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. Moreover, it is becoming more apparent with additional studies that statins can have deleterious effects in preclinical studies and lack effectiveness in various recent clinical trials. This perspective paper outlines pros and cons of the use of statins in neurodegenerative disorders, with particular emphasis on Alzheimer disease.
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington, KY 40506, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA. dabcns@uky.edu
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
authors.forename: Eugenio
authors.initials: E
authors.lastname: Barone
authors.forename: Cesare
authors.initials: C
authors.lastname: Mancuso
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D000069059:Atorvastatin; D002784:Cholesterol / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D005464:Fluorobenzenes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008148:Lovastatin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D005229:Fatty Acids, Monounsaturated; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011743:Pyrimidines; D011758:Pyrroles; D011804:Quinolines; D013449:Sulfonamides; D000077340:Fluvastatin; D000068718:Rosuvastatin Calcium; D002784:Cholesterol; D008148:Lovastatin; D000069059:Atorvastatin; C108475:pitavastatin