Frontiers in Medicinal Chemistry

Volume: 1

Indexed in: Scopus, EMBASE, Chemical Abstracts, EBSCO, Ulrich's Periodicals Directory.

Frontiers in Medicinal Chemistry is a book series devoted to the review of areas of important topical interest to medicinal chemists and others in allied disciplines. Frontiers in Medicinal Chemistry ...
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Emerging β-Amyloid Therapies for the Treatment of Alzheimer's Disease

Pp. 361-384 (24)

Kelly A. Conway, Ellen W. Baxter, Kevin M. Felsenstein and Allen B. Reitz

Abstract

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder marked by loss of memory, cognition, and behavioral stability. AD is defined pathologically by extracellular neuritic plaques comprised of fibrillar deposits of b-amyloid peptide (Ab) and neurofibrillary tangles comprised of paired helical filaments of hyperphosphorylated tau. Current therapies for AD, such as cholinesterase inhibitors, treat the symptoms but do not modify the progression of the disease. The etiology of AD is unclear. However, data from familial AD mutations (FAD) strongly support the “amyloid cascade hypothesis” of AD, i.e. that neurodegeneration in AD is initiated by the formation of neurotoxic b-amyloid (Ab) aggregates; all FAD mutations increase levels of Ab peptide or density of Ab deposits. The likely link between Ab aggregation and AD pathology emphasizes the need for a better understanding of the mechanisms of Ab production. This review summarizes current therapeutic strategies directed at lowering Ab levels and decreasing levels of toxic Ab aggregates through (1) inhibition of the processing of amyloid precursor protein (APP) to Ab peptide, (2) inhibition, reversal or clearance of Ab aggregation, (3) cholesterol reduction and (4) Ab immunization.

Affiliation:

Drug Discovery Division, Johnson & Johnson Pharmaceutical Research and Development, Spring House, PA 19477, USA