Alzheimer's disease therapeutics: new approaches to an ageing problem.
Abnormal proteinaceous deposits are found in the brain of patients with many different neurodegenerative diseases. In many of these diseases, the production of the deposits is probably associated with disease pathogenesis. In Alzheimer's disease (AD), the amyloid protein (A beta), is produced by the action of enzymes known as secretases, which cleave the beta-amyloid protein precursor. A beta is secreted from cells in the brain, after which it oligomerizes and is deposited in the extracellular compartment of the brain to form amyloid plaques and amyloid angiopathy. Targeting the production of A beta and its aggregation is now a key strategy in the development of novel therapeutic agents for the treatment of AD. This review examines the potential of immunization strategies, cholesterol-lowering drugs, protease inhibitors and nicotinic drugs for the treatment of AD.
Small
David H
DH
Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia. david.small@med.monash.edu.au
Losic
Dusan
D
Martin
Lisandra L
LL
Turner
Bradley J
BJ
Friedhuber
Anna
A
Aguilar
Marie-Isabel
MI
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D011978:Receptors, Nicotinic / Q000737:chemistry
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D011978:Receptors, Nicotinic