Roles of p75NTR in the pathogenesis of Alzheimer's disease: a novel therapeutic target

Alzheimer's disease (AD), the most common form of dementia, is characterized by the deposition of amyloid plaques, accumulation of fibrillary tangles in neurons, neurite degeneration, loss of neurons, and a progressive loss of cognitive function. The pathogenesis of AD is not fully understood, and no strong disease-modifying therapies are currently available. Recent studies suggest that the pan-neurotrophin receptor, p75NTR, is a critical factor involved in the pathogenesis of AD. In this review, we have discussed the roles of p75NTR in the production of amyloid-beta (Aβ), neuronal death, neurite degeneration, tau hyperphosphorylation, cell cycle re-entry and cognition decline in AD, and proposed that p75NTR is a potential target for the development of therapeutic drugs for AD. Finally we provide perspectives in developing various therapeutic strategies targeting different aspects of AD hallmarks which relate to p75NTR functions and breaking the p75NTR-mediated positive feedback loop which promotes the cascades in the pathogenesis of AD.