Therapeutic Potential of Secreted Amyloid Precursor Protein APPsα.
Therapeutic Potential of Secreted Amyloid Precursor Protein APPsα.
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DOI：
10.3389/fnmol.2017.00030
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发表时间：
2017
影响因子：
4.8
通讯作者：
Müller UC
中科院分区：
文献类型：
--
作者：
Mockett BG;Richter M;Abraham WC;Müller UC
α-分泌酶对淀粉样蛋白前体蛋白（APP）的裂解产生胞外释放片段，称为分泌型APP- α (APPsα)。这一过程不仅是由于淀粉样蛋白- β序列中APP的裂解，而且APPsα本身具有许多生理特性，表明其作为治疗靶点的巨大潜力。例如，APPsα具有神经营养、神经保护、神经原性，是蛋白质合成和基因表达的刺激物，并能增强长期增强（LTP）和记忆。虽然大多数早期研究都是在体外进行的，但现在正在证实动物模型的有效性。这些研究表明，上调α-分泌酶活性、急性给予APPsα或通过基因治疗方法慢性给予APPsα均可有效治疗阿尔茨海默病（AD）和其他疾病（如创伤性脑损伤）的小鼠模型。总之，这些发现表明需要加强研究工作，以利用这种多功能蛋白的治疗潜力。
Cleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage of APP within the amyloid-beta sequence, but APPsα itself has many physiological properties that suggest its great potential as a therapeutic target. For example, APPsα is neurotrophic, neuroprotective, neurogenic, a stimulator of protein synthesis and gene expression, and enhances long-term potentiation (LTP) and memory. While most early studies have been conducted in vitro, effectiveness in animal models is now being confirmed. These studies have revealed that either upregulating α-secretase activity, acutely administering APPsα or chronic delivery of APPsα via a gene therapy approach can effectively treat mouse models of Alzheimer’s disease (AD) and other disorders such as traumatic head injury. Together these findings suggest the need for intensifying research efforts to harness the therapeutic potential of this multifunctional protein.