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at various websites: Alzheimer Research Forum; individual drug company databases; Medline; Pharmaprojects database; unpublished research; inter-University research communications.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.
Lukiw
Walter J
WJ
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
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