Rockenstein E, Mallory M, Mante M, Alford M, Windisch M, Moessler H, Masliah E
Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA 92093-0624, USA.
J Neural Transm Suppl. 2002(62):327-36.
We investigated the potential mechanisms through which Cerebrolysin, a neuroprotective noothropic agent, might affect Alzheimer's disease pathology. Transgenic (tg) mice expressing mutant human (h) amyloid precursor protein 751 (APP751) cDNA under the Thy-1 promoter (mThy1-hAPP751) were treated for four weeks with this compound and analyzed by confocal microscopy to asses its effects on amyloid plaque formation and neurodegeneration. In this model, amyloid plaques in the brain are found much earlier (beginning at 3 months) than in other tg models. Quantitative computer-aided analysis with anti-amyloid-beta protein (A beta) antibodies, revealed that Cerebrolysin significantly reduced the amyloid burden in the frontal cortex of 5-month-old mice. Furthermore, Cerebrolysin treatment reduced the levels of A beta(1-42). This was accompanied by amelioration of the synaptic alterations in the frontal cortex of mThy1-hAPP751 tg mice. In conclusion, the present study supports the possibility that Cerebrolysin might have neuroprotective effects by decreasing the production of A beta(1-42) and reducing amyloid deposition.
我们研究了脑蛋白水解物(一种具有神经保护作用的益智药)可能影响阿尔茨海默病病理的潜在机制。用该化合物对在Thy-1启动子(mThy1-hAPP751)控制下表达突变型人淀粉样前体蛋白751(APP751)cDNA的转基因(tg)小鼠进行了为期四周的治疗,并通过共聚焦显微镜分析来评估其对淀粉样斑块形成和神经退行性变的影响。在这个模型中,大脑中的淀粉样斑块比其他tg模型出现得更早(从3个月开始)。用抗β淀粉样蛋白(Aβ)抗体进行的定量计算机辅助分析显示,脑蛋白水解物显著降低了5月龄小鼠额叶皮质中的淀粉样蛋白负荷。此外,脑蛋白水解物治疗降低了Aβ(1-42)的水平。这伴随着mThy1-hAPP751 tg小鼠额叶皮质中突触改变的改善。总之,本研究支持脑蛋白水解物可能通过减少Aβ(1-42)的产生和减少淀粉样蛋白沉积而具有神经保护作用的可能性。