Gelsolin is Proteolytically Cleaved in the Brains of Individuals with Alzheimer's Disease
Gelsolin is Proteolytically Cleaved in the Brains of Individuals with Alzheimer's Disease
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DOI：
10.3233/jad-2009-1127
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发表时间：
2009-01-01
影响因子：
4
通讯作者：
Chauhan, Ved
中科院分区：
文献类型：
--
作者：
Ji, Lina;Chauhan, Abha;Chauhan, Ved
凝溶胶蛋白是一种多功能肌动蛋白结合蛋白，与淀粉样β蛋白形成复合物，并降低阿尔茨海默病（AD）转基因小鼠模型中的淀粉样蛋白负荷。凝溶胶蛋白由六个同源结构域组成，它们对磷脂酰肌醇4，5-二磷酸、钙和肌动蛋白具有特异性亲和力。在细胞凋亡过程中，凝溶胶蛋白被半胱天冬酶-3切割，产生48 kDa羧基末端片段（凝溶胶蛋白-CTF）。我们在这里报告说，凝溶胶蛋白显着分裂的前额叶皮层的个人与AD相比，年龄匹配的控制。额皮质凝溶胶蛋白-CTF的出现与AD的严重程度呈正相关。在H2 O2或钙离子载体A23187诱导的SH-SY 5 Y细胞凋亡中也观察到凝溶胶蛋白-CTF。此外，AD患者额叶皮质脂质过氧化反应增强，提示AD脑内存在氧化应激。两者合计，这些结果表明，有可能是一个链接之间的氧化应激，神经元凋亡，凝溶胶蛋白裂解在AD。
Gelsolin, a multifunctional actin-binding protein, forms a complex with amyloid-beta protein and reduces the amyloid load in the transgenic mouse model of Alzheimer's disease (AD). Gelsolin consists of six homologous domains, which have specific affinities for phosphatidylinositol 4, 5-bisphosphate, calcium, and actin. During apoptosis, gelsolin is cleaved by the caspase-3 resulting in a 48 kDa carboxyl-terminal fragment (gelsolin-CTF). We report here that gelsolin is significantly cleaved in the frontal cortex of individuals with AD as compared to age-matched controls. A positive correlation was observed between the appearance of gelsolin-CTF in frontal cortex and severity of AD. Gelsolin-CTF was also observed in apoptotic SH-SY5Y cells induced by H2O2 or calcium ionophore A23187. In addition, lipid peroxidation was increased in the frontal cortex of AD suggesting that oxidative stress occurs in AD brain. Taken together, these results suggest that there may be a link among oxidative stress, neuronal apoptosis, and gelsolin cleavage in AD.