Beta-site APP cleaving enzyme 1 (BACE1) is increased in remaining neurons in Alzheimer's disease brains
Beta-site APP cleaving enzyme 1 (BACE1) is increased in remaining neurons in Alzheimer's disease brains
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DOI：
10.1016/j.neures.2005.10.001
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发表时间：
2006-01-01
影响因子：
2.9
通讯作者：
Murayama, S
中科院分区：
文献类型：
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作者：
Harada, H;Tamaoka, A;Murayama, S
阿尔茨海默病（AD）的特征在于淀粉样β蛋白（A β）在大脑皮层中的广泛沉积。β-淀粉样前体蛋白（APP）通过β-分泌酶和γ-分泌酶产生β。β-Secretase被鉴定为β位点APP裂解酶I（BACE I）。使用这些抗体，BACE 1的特点是在颞叶皮质蛋白质印迹和免疫组化。用抗GFAP、MAP 2及其抗BACE 1的抗体进行免疫组织化学染色，结果显示BACE 1只在神经元表达，而在胶质细胞中不表达。AD患者脑组织中BACE 1/mg蛋白的平均水平虽未升高，但BACE 1/MAP 2和/NSE的比值均显著高于对照组，提示AD患者脑组织中存活的神经元可能比正常神经元产生更多的BACE I，提示BACE 1活性升高可能是AD的病因之一。这可能证明开发用于AD治疗的抗BACE 1药物是合理的。(c)2005年Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
Alzheimer's disease (AD) is characterized by the extensive deposition of amyloid beta protein (A beta) in the brain cortex. A beta is produced from beta-amyloid precursor protein (APP) by beta-secretase and gamma-secretase. beta-Secretase has been identified as beta-site APP cleaving enzyme I (BACE I), We produced rabbit polyclonal antibodies against the amino and the carboxyl terminals of BACE1. Using these anti bodies, BACE1 was characterized in temporal lobe cortices by Western blotting and immunohistochemistry. Immumohistochemical studies employing anti-GFAP and anti-MAP2 antibodies as well its anti-BACE1 antibodies showed that BACE1 was expressed exclusively in neurons but not in glial cells.Brain samples were directly extracted by 0.5% SDS and analyzed by Western blotting and densitometer. Although the mean level of BACE 1/mg protein in AD brains was not increased, the ratio of BACE1 to MAP2 or to NSE was significantly increased compared with that in control brains.Taken together, these findings suggest that those neurons that survive in AD brains might generate more BACE I than normal neurons in control brains, indicating that increased BACE1 activity could be one of the causes of AD. This could justify the development of anti-BACE1 drugs for AD treatment. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.