Signaling of the neurotrophin receptor p75 in relation to Alzheimer's disease.

The cellular mechanism of neuronal apoptosis in Alzheimer's disease (AD) is poorly understood. Many hypotheses have been put fourth to explain the underlying reason for neuro-degeneration in AD. Here, it is demonstrated that all neurotrophins that activated p75, without co-activation of the relevant Trk co-receptor, mediated apoptosis in hippocampal neurons. Thus, proneurotrophins and amyloid beta peptides (Abeta) can induce p75-mediated apoptosis in hippocampal neurons since they do not bind or activate Trk receptors. Based on the combined effects of aging, proneurotrophins, neurotrophins, and Abeta, a novel model of pathogenesis in AD is proposed. This mini-review explores the ligand and cell type based signaling pathways of the neurotrophin receptor p75 relating to Alzheimer's disease.