Antón Álvarez X, Fuentes Patricio
EuroEspes Biomedical Research Centre, A Coruña, Spain.
Drugs Today (Barc). 2011 Jul;47(7):487-513. doi: 10.1358/dot.2011.47.7.1656496.
Cerebrolysin is a neuropeptide preparation mimicking the action of endogenous neurotrophic factors. Positive effects of Cerebrolysin on β-amyloid- and tau-related pathologies, neuroinflammation, neurotrophic factors, oxidative stress, excitotoxicity, neurotransmission, brain metabolism, neuroplasticity, neuronal apoptosis and degeneration, neurogenesis and cognition were demonstrated in experimental conditions. These pleiotropic effects of Cerebrolysin on Alzheimer's disease-related pathogenic events are consistent with a neurotrophic-like mode of action, and seems to involve the activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 β intracellular signaling pathway. The clinical efficacy of Cerebrolysin in Alzheimer's disease was evaluated in several randomized, double-blind, clinical trials, showing consistent benefits on global clinical function and cognition, improvements in behavior at high doses, and minor effects on daily living activities in patients with mild to moderate Alzheimer's disease, as well as in subgroups of moderate to moderately severe patients. In addition, the clinical benefits of Cerebrolysin were largely maintained for several months after ending treatment, a finding that supports its discontinuous administration. Cerebrolysin was generally well tolerated and did not induce significant adverse events in Alzheimer's patients. Although long-term studies are needed, the data available suggest that Cerebrolysin is effective as monotherapy and constitutes a promising option for combined therapy in Alzheimer's disease.
脑蛋白水解物是一种模拟内源性神经营养因子作用的神经肽制剂。在实验条件下已证实脑蛋白水解物对β-淀粉样蛋白和tau相关病理、神经炎症、神经营养因子、氧化应激、兴奋性毒性、神经传递、脑代谢、神经可塑性、神经元凋亡和变性、神经发生及认知具有积极作用。脑蛋白水解物对阿尔茨海默病相关致病事件的这些多效性作用与神经营养样作用模式一致,且似乎涉及磷脂酰肌醇3激酶/蛋白激酶B/糖原合酶激酶-3β细胞内信号通路的激活。在多项随机、双盲临床试验中评估了脑蛋白水解物在阿尔茨海默病中的临床疗效,结果显示其对整体临床功能和认知具有持续益处,高剂量时行为有所改善,对轻度至中度阿尔茨海默病患者以及中度至中度重度患者亚组的日常生活活动有轻微影响。此外,在治疗结束后的几个月里,脑蛋白水解物的临床益处基本得以维持,这一发现支持其间断给药。脑蛋白水解物在阿尔茨海默病患者中总体耐受性良好,未引发明显不良事件。尽管需要长期研究,但现有数据表明脑蛋白水解物作为单一疗法有效,是阿尔茨海默病联合治疗的一个有前景的选择。