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Specifically, while transient activation of CRF1-Gs-PKA shifts APP metabolism towards the α-secretase-mediated pathway that results in non-pathogenic amyloids, chronic activation of these signaling cascades shifts APP metabolism to the β-, γ−secretase, and perhaps also η-secretase mediated pathways that result in increased pathogenic Aβ generation (da Cruz e Silva et al., 2009; Willem et al., 2015).
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