Amyloid beta modulators and neuroprotection in Alzheimer's disease: a critical appraisal

Multiple cellular changes have been identified as being involved in Alzheimer's disease (AD) pathogenesis, including mitochondrial damage, synaptic loss, amyloid beta (A beta) production and/or accumulation, inflammatory responses, and phosphorylated tau formation and/or accumulation. Studies have established that A beta-induced synaptic dysfunction is dependent on abnormal amyloid precursor protein (APP) processing caused by beta- and gamma-secretases, resulting in the generation of A beta. The A beta formed as a result of abnormal APP processing induces phosphorylated tau and activates glycogen synthase kinase-3 beta (GSK3 beta) and cyclin-dependent kinase-5 (CDK5). Here, we review the latest research on the development of A beta modulators for neuroprotection in AD. We also review the use of molecular inhibitors as therapeutic targets in AD.