A complex disease such as Alzheimer’s requires an arsenal of therapies to
help combat and stabilize its advancement. Despite considerable scientific progress,
current therapeutic approaches for Alzheimer’s treatment offer only limited and
transient benefits to patients. Therefore, in response to the molecular complexity of this
disease, a new strategy has recently emerged aimed at simultaneously targeting multiple
pathological processes involved in the pathogenesis cascade. β-secretase plays a critical
role in β-amyloid formation, a major constituent of amyloid plaques in Alzheimer’s
disease (AD) brain and is likely to play a central role in the pathogenesis of this
devastating neurodegenerative disorder. Thus, β-secretase is a prime drug target for the
therapeutic inhibition of β-amyloid production in AD. It has been clearly established in
a number of studies that metal ions are critically involved in the pathogenesis and
progression of major neurological diseases (Alzheimer's, Parkinson's). Metal ion
chelators have been suggested as potential therapies for diseases involving metal ion
imbalance. This chapter summarizes the current therapeutic strategies based on the
β-secretase inhibition, metal chelation and their combination to treat AD.
Keywords: Aβ aggregation, Alzheimer’s disease, amino imidazoles, amyloid beta
precursor protein, amyloid plaque, Bi-functional compounds, clinical development,
cyclic hydroxyethylamines, dementia, fragment-based lead generation, highthroughput
screening, metal chelators, multi-targeted drugs, neurodegenerative
disorders, oxidative stress, peptidomimetics, reactive oxygen species, substratebased
design, β-secretase (BACE1), γ-secretase.
