New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
J Alzheimers Dis. 2009;18(1):105-11. doi: 10.3233/JAD-2009-1127.
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.
凝溶胶蛋白是一种多功能的肌动蛋白结合蛋白，它与淀粉样β蛋白形成复合物，从而减少阿尔茨海默病（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，这些结构域对磷脂酰肌醇 4,5-二磷酸、钙和肌动蛋白具有特定的亲和力。在细胞凋亡过程中，半胱氨酸蛋白酶-3 对凝溶胶蛋白进行切割，形成 48 kDa 的羧基末端片段（凝溶胶蛋白 CTF）。我们在这里报告，与年龄匹配的对照组相比，AD 患者的大脑额叶中凝溶胶蛋白的切割明显增加。在 AD 患者的大脑额叶中，观察到凝溶胶蛋白 CTF 的出现与 AD 的严重程度呈正相关。在过氧化氢或钙离子载体 A23187 诱导的 SH-SY5Y 细胞凋亡中也观察到了凝溶胶蛋白 CTF。此外，AD 患者大脑额叶中的脂质过氧化增加，表明 AD 大脑中存在氧化应激。综上所述，这些结果表明，氧化应激、神经元凋亡和 AD 中的凝溶胶蛋白切割之间可能存在联系。
