Peptides homologous to the amyloid protein of Alzheimer's disease containing a glutamine for glutamic acid substitution have accelerated amyloid fibril formation.
Peptides homologous to the amyloid protein of Alzheimer's disease containing a glutamine for glutamic acid substitution have accelerated amyloid fibril formation.
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DOI：
10.1016/0006-291x(91)91706-i
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发表时间：
1991-09
影响因子：
3.1
通讯作者：
T. Wisniewski;J. Ghiso;B. Frangione
中科院分区：
文献类型：
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作者：
T. Wisniewski;J. Ghiso;B. Frangione
淀粉样蛋白(β-β，A-A)沉积是许多疾病的中心事件，包括阿尔茨海默病(AD)和遗传性脑出血伴淀粉样变性-荷兰型(HcHWA-D)。β是由较大的淀粉样前体蛋白(APP)降解产生的。最近，在HCHWA-D中发现了APP基因的突变，导致Aβ第22位的谷氨酰胺取代谷氨酸。这种突变对纤维形成的影响尚不清楚，尽管很明显，受影响的患者加速了脑血管淀粉样蛋白的沉积，并在生命早期出现疾病症状。我们报道了在28个与荷兰变种Aβ同源的合成多肽中加速纤维形成的体外演示。此外，在与Aβ同源的8个残基肽中，突变的存在是形成纤维所必需的。这些发现为荷兰变种APP中淀粉样蛋白的加速形成提供了一种机制。
β-Amyloid (Aβ) deposition in fibril form is the central event in a number of diseases, including Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis — Dutch type (HCHWA-D). Aβ is produced by degradation of a larger amyloid precursor protein (APP). Recently a mutation in the APP gene has been found in HCHWA-D causing a glutamine for glutamic acid substitution at residue 22 of Aβ. The influence of this mutation on fibrillogenesis is not known, although it is clear that affected patients have accelerated cerebrovascular amyloid deposition, with disease symptoms early in life. We report thein vitrodemonstration of accelerated fibril formation in a 28 resdue synthetic peptide homologous to the Dutch variant Aβ. Furthermore, in eight residue peptides homologous to Aβ the presence of the mutation is necessary for fibril formation. These findings provide a mechanism for accelerated amyloid formation in the Dutch variant of APP.