gamma-secretase substrateのプロテオーム解析

抄録

Alzheimer's disease is an age-dependent neurodegenerative disorder which is characterized by a progressive decline in cognitive function. Gamma-secretase dysfunction is evident in many cases of early-onset familial Alzheimer's disease. However, the mechanism by which gamma-secretase dysfunction results in memory loss and neurodegeneration is not fully understood. In this study, we performed a proteomic analysis of gamma-secretase substrates and identified EphA4 as a novel substrate. Moreover, we found that overexpression of EphA4 intracellular domain increased the number of dendritic spines by activating the Rac signaling pathway. These findings suggest that the processing of EphA4 by gamma-secretase affects the pathogenesis of Alzheimer's disease.