首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Concerted action of dipeptidyl peptidase IV and glutaminyl cyclase results in formation of pyroglutamate-modified amyloid peptides in vitro
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Concerted action of dipeptidyl peptidase IV and glutaminyl cyclase results in formation of pyroglutamate-modified amyloid peptides in vitro

机译:二肽肽肽酶IV和谷氨酸环酶的齐齐异作用导致在体外形成吡酰磺酸盐改性的淀粉样蛋白肽

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摘要

Compelling evidence suggests a crucial role of amyloid beta peptides (A beta(1-40/42)) in the etiology of Alzheimer's disease (AD). The N-terminal truncation of A beta(1-40/42) and their modification, e.g. by glutaminyl cyclase (QC), is expected to enhance the amyloid toxicity. In this work, the MALDI-TOF mass spectrometry application proved N-terminal cleavage of A beta(1-40/42) by purified dipeptidyl peptidase IV (DPPIV) in vitro observed earlier. The subsequent transformation of resulted A beta(3-40/42) to pE-A beta(3-40/42) in QC catalyzed glutamate cyclization was manifested. Hence, consecutive conversion of A beta(1-40/42) by DPPIV and QC can be assumed as a potential mechanism of formation of non-degrading pyroglutamated pE-A beta(3-40/42), which might accumulate and contribute to AD progression. The in vitro acceleration of A beta(1-40) aggregation in the simultaneous presence of DPPIV and QC was shown also. (C) 2017 Published by Elsevier Ltd.
机译:令人信服的证据表明淀粉样蛋白β肽(β(1-40 / 42))在阿尔茨海默病的病因(AD)中的关键作用。 β(1-40 / 42)的N-末端截短及其修改,例如, 通过谷氨酰胺环酶(QC),预期增强淀粉样蛋白毒性。 在这项工作中,MALDI-TOF质谱施用通过纯化的二肽基肽酶IV(DPPIV)以前观察到的纯化的二肽基肽酶IV(DPPIV)证明了β(1-40 / 42)的N-末端切割。 表现出后续转化的β(3-40 / 42)在QC催化谷氨酸环化中的PE-Aβ(3-40 / 42)的转化。 因此,通过DPPIV和QC的β(1-40 / 42)的连续转化可以假定为形成非降解的焦蛋白的PE-Aβ(3-40 / 42)的潜在机制,这可能会积累和贡献 广告进展。 还显示了在DPPIV和QC同时存在下β(1-40)聚集的体外加速。 (c)2017年由elestvier有限公司出版

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