Institute of Biochemistry, Johannes Gutenberg-University, Johann-Joachim-Becherweg 30, D-55128 Mainz, Germany.
Neurobiol Dis. 2009 Nov;36(2):233-41. doi: 10.1016/j.nbd.2009.07.015. Epub 2009 Jul 24.
Both the cellular prion protein (PrP(c)) and the amyloid precursor protein (APP) are physiologically subjected to complex proteolytic processing events. While for APP the proteinases involved--alpha-, beta- and gamma-secretase--have been identified in vitro and in vivo, the cleavage of PrP(c) by now has been linked only to the shedding activity of the metalloproteinase ADAM10 and/or ADAM17 in cell culture. Here we show that neuronal overexpression of the alpha-secretase ADAM10 in mice reduces all PrP(c) species detected in the brain instead of leading to enhanced amounts of specific cleavage products of PrP(c). Additionally, the incubation time of mice after scrapie infection is significantly increased in mice moderately overexpressing ADAM10. This indicates that overexpression of ADAM10 rather influences the amount of the cellular prion protein than its processing in vivo.
细胞朊蛋白 (PrP(c)) 和淀粉样前体蛋白 (APP) 在生理上都受到复杂的蛋白水解加工事件的影响。虽然 APP 涉及的蛋白酶——α-、β-和 γ-分泌酶——已经在体外和体内被鉴定出来，但 PrP(c) 的切割迄今为止仅与金属蛋白酶 ADAM10 和/或 ADAM17 在细胞培养中的脱落活性有关。在这里，我们表明，在小鼠中过表达 α-分泌酶 ADAM10 会减少大脑中检测到的所有 PrP(c) 物种，而不是导致 PrP(c) 的特定切割产物的量增加。此外，在中度过表达 ADAM10 的小鼠中，感染朊病毒后小鼠的孵育时间显著增加。这表明 ADAM10 的过表达与其在体内的加工相比，更能影响细胞朊蛋白的数量。
