Disease modifying strategies for the treatment of Alzheimer's disease targeted at modulating levels of the beta-amyloid peptide.
AD (Alzheimer's disease) is characterized neuropathologically by the presence of amyloid plaques, neurofibrillary tangles and profound grey matter loss. The 'amyloid' hypothesis postulates that the toxic Abeta (amyloid beta) peptide, enzymatically derived from the proteolytic processing of a larger protein called APP (amyloid precursor protein), is one of the principal causative factors of neuronal cell death in the brains of AD patients. As such, methods for lowering Abeta levels in the brain are of significant interest with regard to identifying novel disease modifying therapies for the treatment of AD. In this review, we will review a variety of approaches and mechanisms capable of modulating levels of Abeta.
Pangalos
M N
MN
Wyeth Research, Neuroscience Discovery Research, Princeton, NJ 08543, USA. PANGALM@wyeth.com
Jacobsen
S J
SJ
Reinhart
P H
PH
D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy*; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D007114:Immunization; D011499:Protein Processing, Post-Translational
D016229:Amyloid beta-Peptides; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human