Glycogen synthase kinase 3 beta and Alzheimer's disease: pathophysiological and therapeutic significance

Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the serine-threonine kinase, glycogen synthase kinase beta(GSK-3 beta) in the pathogenesis of AD. GSK-3 beta may play an important role in the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review, we discuss the interaction between GSK-3 beta and several key molecules involved in AD, including the presenilins, amyloid precursor protein, tau, and beta-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt, Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD.