Walter J Lukiw1. 1. 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
Abstract
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at various websites: Alzheimer Research Forum; individual drug company databases; Medline; Pharmaprojects database; unpublished research; inter-University research communications. RESULTS/ CONCLUSION: 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.
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 humanbrain 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at various websites: Alzheimer Research Forum; individual drug company databases; Medline; Pharmaprojects database; unpublished research; inter-University research communications. RESULTS/ CONCLUSION: 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.
Authors: Francesco Panza; Vincenzo Solfrizzi; Vincenza Frisardi; Cristiano Capurso; Alessia D'Introno; Anna M Colacicco; Gianluigi Vendemiale; Antonio Capurso; Bruno P Imbimbo Journal: Drugs Aging Date: 2009 Impact factor: 3.923