Tat peptides inhibit neprilysin
Tat peptides inhibit neprilysin
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DOI：
10.1080/13550280600760677
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发表时间：
2006-06-01
影响因子：
3.2
通讯作者：
Hersh, Louis B.
中科院分区：
文献类型：
--
作者：
Daily, Abigail;Nath, Avindra;Hersh, Louis B.
与人类免疫缺陷病毒（HIV）感染相关的痴呆症通常发生在老年人群中，并且在较年轻年龄组的HIV感染患者的大脑中注意到淀粉样蛋白沉积。这表明在HIV感染的情况下淀粉样蛋白的加工失调。HIV的达特蛋白由于其神经毒性和胶质活化特性而与HIV感染的神经发病机制有关。然而，最近还显示达特蛋白和塔特衍生肽在细胞聚集体系统中抑制脑啡肽酶（脑中主要的淀粉样β肽降解酶）。这种效应可能有助于观察到的HIV感染患者大脑中淀粉样蛋白的积累。作者在此报道，来自达特蛋白的肽，而不是达特蛋白本身，抑制同源重组脑啡肽酶。这种抑制被认为是竞争性的和可逆的，因此不涉及共价键的形成。达特肽和达特蛋白被脑啡肽酶缓慢水解。因此，Tat衍生的蛋白水解片段的积累可用于抑制脑啡肽酶并增加淀粉样蛋白β肽水平。
Dementia associated with human immunodeficiency virus (HIV) infection occurs commonly in the aging population and amyloid depositions are noted in the brains of patients with HIV infection in younger age groups. This suggests a dysregulation of amyloid processing in the setting of HIV infection. The Tat protein of HIV has been implicated in the neuropathogenesis of HIV infection due to its neurotoxic and glial activation properties. However, Tat protein and Tat-derived peptides were recently also shown to inhibit neprilysin, the major amyloid beta peptide degrading enzyme in brain, in a cell aggregate system. This effect could contribute to the observed accumulation of amyloid in the brain of HIV-infected patients. The authors report here that peptides derived from the Tat protein, but not Tat protein itself, inhibit homogeneous recombinant neprilysin. This inhibition was found to be competitive and reversible and therefore does not involve covalent bond formation. Tat peptides and Tat protein were slowly hydrolyzed by neprilysin. Thus the accumulation of Tat-derived proteolytic fragments may serve to inhibit neprilysin and increase amyloid beta peptide levels.