p75NTR: A molecule with multiple functions in amyloid-beta metabolism and neurotoxicity

Abstract

The p75 neurotrophin receptor (p75NTR) is a pan-receptor for neurotrophins including nerve growth factor, brain-derived neurotrophic factor, neurotrophin- 3, and neurotrophin 4/5. P75NTR plays a diverse role from regulating cell survival to modulating neurite outgrowth. Under some pathological conditions, p75NTR expression is activated and plays detrimental roles in disease progression. 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. Recent studies suggest that p75NTR, also a receptor for amyloid-beta (Aß), is a critical factor involved in the pathogenesis of AD. This chapter is to discuss the roles of p75NTR in the production of amyloidbeta (Aß), neuronal death, neurite degeneration, tau hyperphosphorylation, cell cycle re-entry, and cognition decline, to propose that p75NTR is a potential target for the development of therapeutic drugs for AD, and to 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.