Abstract
Amyloid-β precursor protein (APP) is well studied for its role in Alzheimer disease, although its normal function remains uncertain. It has been reported that APP stimulates the proliferation and neuronal differentiation of neural stem/progenitor cells (NSPCs). In this study we examined the role of APP in NSPC differentiation. To identify proteins that may mediate the effect of APP on NSPC differentiation, we used a gene array approach to find genes whose expression correlated with APP-induced neurogenesis. We found that the expression of neurogenin 2 (Ngn2), a basic helix-loop-helix transcription factor, was significantly down-regulated in NSPCs from APP knock-out mice (APPKO) and increased in APP transgenic (Tg2576) mice. Ngn2 overexpression in APPKO NSPCs promoted neuronal differentiation, whereas siRNA knockdown of Ngn2 expression in wild-type NSPCs decreased neuronal differentiation. The results demonstrate that APP-stimulated neuronal differentiation of NSPCs is mediated by Ngn2.
Highlights
Amyloid- precursor protein is implicated in neural stem cell development
We previously found that neural stem/progenitor cells (NSPCs) derived from Tg2576 mice, which overexpress Amyloid- precursor protein (APP), possessed a greater potential to differentiate into neurons, whereas cells derived from APP-knock-out (APPKO) mice exhibited decreased neuronal differentiation [19]
The present study shows that neuronal differentiation is lower in NSPCs derived from APP knock-out mice (APPKO) mice and that this effect is due to decreased expression of neurogenin 2 (Ngn2)
Summary
Amyloid- precursor protein is implicated in neural stem cell development. Results: Neurogenin 2 expression and neuronal differentiation correlated with amyloid- precursor protein expression in neural stem/progenitor cells. Conclusion: Amyloid- precursor protein regulates neuronal differentiation by altering neurogenin 2 expression. Significance: The study provides a new mechanism to explain the effects of amyloid- precursor protein on neural stem cell differentiation. Amyloid- precursor protein (APP) is well studied for its role in Alzheimer disease, its normal function remains uncertain. It has been reported that APP stimulates the proliferation and neuronal differentiation of neural stem/progenitor cells (NSPCs). APP may play a role in promoting the differentiation of NSPCs. APP expression increases as NSPCs mature into neurons [26], and soluble APP has been reported to promote neural differentiation [27, 28]. We demonstrate that the neuronal differentiation of NSPCs, induced by APP, is mediated by neurogenin 2 (Ngn2)
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