Isoprenoids and Alzheimer's disease: a complex relationship.
Cholesterol metabolism has been linked to Alzheimer's disease (AD) neuropathology, which is characterized by amyloid plaques, neurofibrillary tangles and neuroinflammation. Indeed, the use of statins, which inhibit cholesterol and isoprenoid biosynthesis, as potential AD therapeutics is under investigation. Whether statins offer benefit for AD will be determined by the outcome of large, placebo-controlled, randomized clinical trials. However, their use as pharmacological tools has delineated novel roles for isoprenoids in AD. Protein isoprenylation regulates multiple cellular and molecular events and here we review the complex roles of isoprenoids in AD-relevant processes and carefully evaluate isoprenoid pathways as potential AD therapeutic targets.
Cole
S L
SL
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611, USA. s-cole4@northwestern.edu
Vassar
R
R
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002784:Cholesterol / Q000096:biosynthesis*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism; D017368:Protein Prenylation / Q000187:drug effects* / Q000502:physiology; D013729:Terpenes / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013729:Terpenes; D002784:Cholesterol