Amyloid precursor protein (APP) is a transmembrane glycoprotein proteolytically processed to release amyloid beta, a pathological hallmark of Alzheimer’s disease. APP is expressed throughout the developing and mature brain. However, the primary function of this protein is unknown.
It’s demonstrated previously that APP deficiency enhances neurogenesis, but the mechanisms underlying this process are not known. The scientists showed that APP regulates the expression of microRNAs in the cortex and in neural progenitors, specifically repressing miR-574-5p. And they also showed that overexpression of miR-574-5p promotes neurogenesis, but reduces the neural progenitor pool. In contrast, the reduced expression of miR-574-5p inhibits neurogenesis and stimulates proliferation in vitro and in utero. Furthermore they demonstrated that the inhibition of miR-574-5p in APP-knockout mice rescues the phenotypes associated with APP deficiency in neurogenesis. Taken these together, their results reveal a mechanism in which APP regulates the neurogenesis through miRNA-mediated post-transcriptional regulation.
Zhang W, Thevapriya S, Kim PJ, Yu WP, Shawn Je H, King Tan E, Zeng L. Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in the developing cerebral cortex. Nature communications. 2014;5:3330.