Emerging amyloid beta (Ab) peptide modulators for the treatment of Alzheimer's disease (AD).
BACKGROUND
According to the 'amyloid cascade hypothesis' of Alzheimer's disease (AD), abnormal processing of beta-amyloid precursor protein (betaAPP) into toxic amyloid beta (Abeta)-peptides is central to the etiopathology of this uniquely human brain disorder.


OBJECTIVE
To review current AD drugs, pharmacological approaches and strategies aimed at modulating Abeta-peptide generation and/or aggregation in the treatment of AD.


METHODS
Data searches at various websites: Alzheimer Research Forum; individual drug company databases; Medline; Pharmaprojects database; unpublished research; inter-University research communications.


CONCLUSIONS
Considerable research effort has focused on secretase-mediated mechanisms of betaAPP processing, and the latest pharmacological strategies have used selective Abeta-peptide-lowering agents (SALA) to provide therapeutic benefit against Abeta-initiated neurodegenerative pathology. Currently, dedicated anticholinesterase, glutamatergic agonist and Abeta-peptide immunization have had little impact in the clinical treatment of AD. One unexpected benefit of statins (HMG-CoA inhibitors), besides their cholesterol lowering abilities, has been their ancillary effects in potentiating the enzymatic mechanisms that generate Abeta-peptides. The long-term benefits or complications of statin-based therapies for use in the clinical management of AD are not known.
Louisiana State University Health Sciences Center, LSU Neuroscience Center of Excellence, 2020 Gravier Street, Suite 8B8, New Orleans, LA 70112-2272, USA. wlukiw@lsuhsc.edu
Walter J
WJ
Lukiw
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007114:Immunization
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors