Development of anti-Alzheimer's drugs and their molecular targets

Alzheimer's disease (AD) is a neurodegenerative disorder that is neuropathologically characterized by the presence of numerous senile plaques and neurofibrillaiy tangles accompanied by neuronal loss. The extracellular senile plaques are composed of amyloid β-peptides (Aβ), 40-42 amino acid peptide fragments of the β-amyloid precursor protein (APP), whereas the intracellular neurofibrillaiy tangles are composed of highly phosphorylated tau proteins. Some forms of familial AD are caused by the inheritance of mutant genes, including genes encoding the amyloid precursor protein (APP) and presenilin 1 (PS1) and 2 (PS2). There is also an association between AD and apolipoprotein E (ApoE) gene. Although the exact pathogenesis of AD remains to be fully defined, several pharmacological strategies for the treatment of AD are under active investigation. These include the cholinergic therapy that is designed to increase cholinergic functions, anti-inflammatory agents and antioxidants. The anti-Aβ strategies in AD, which refer to intervention of the amyloid cascade of the disease, are the most attractive approaches for the treatment of AD. Other possible strategies involve vaccine therapy with Aβ immunization and neurotrophic factor therapy.