APP as an innate injury-response molecule

Amyloid precursor protein (APP) is best known as the percussor for amyloid beta (Aβ), a hallmark of pathology in Alzheimer's disease and related disorders. Nevertheless, APP did not likely evolve to serve this purpose. This article reviews available evidence for functions of APP and its enzymatically generated proteolytic derivatives, sAPPα, CTFα, sAPPβ, CTFβ, p3 peptide, AICD, and Aβ. These functions include not only effects on the development and function of neurons in the central nervous system (CNS), but also innate roles in the response to diverse types of cell and tissue injury in multiple mammalian organ systems including the CNS. These responses include regulation or modulation of hemostasis, inflammation, glial cell functions, antimicrobial defense, and wound healing. We examine how dual, naturally occurring APP roles regarding both neuronal function and injury response, may relate to, and in some cases predispose to, APP-related effects in CNS neurodegenerative disorders.