Hippocampus
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Amyloid precursor protein (APP) is an integral membrane glycoprotein present at high levels in nerve cells. Two soluble secreted forms, sAPPα and sAPPβ, are processed from APP by two mutually exclusive proteolytic pathways. sAPPα shows a range of neuroprotective and growth factor properties, including reduction of neuronal injury and improvement in memory performance, in contrast to the generally less potent sAPPβ. In addition, sAPPα has been shown to increase the proliferation of both embryonic neural stem cells and neural progenitor cells (NPCs) derived from the subventricular zone (SVZ) of the adult brain. ⋯ The effect on differential fate was observed in both the presence and absence of depolarizing conditions. Thus, both sAPPα and sAPPβ exert a complex range of effects on SGZ-derived adult NPCs, including increasing NPC proliferation, maintaining cell viability, yet promoting glial over neuronal differentiation. These findings provide the first direct support for the secreted forms of APP regulating SGZ-derived NPCs, and raise the possibility some or all of the effects may have therapeutic benefit in models of neurological disease.