So far, there is no effective disease-modifying therapies for Alzheimer’s Disease (AD) in clinical practice. In this context, glycine-L-proline-L-glutamate (GPE) and its analogs may open the way for developing a novel molecule for treating neurodegenerative disorders, including AD. In turn, this study was aimed to investigate the neuroprotective potentials exerted by three novel GPE peptidomimetics (GPE1, GPE2, and GPE3) using an in vitro AD model. Anti-Alzheimer potentials were determined using a wide array of techniques, such as measurements of mitochondrial viability (MTT) and lactate dehydrogenase (LDH) release assays, determination of acetylcholinesterase (AChE), α-secretase and β-secretase activities, comparisons of total antioxidant capacity (TAC) and total oxidative status (TOS) levels, flow cytometric and microscopic detection of apoptotic and necrotic neuronal death, and investigating gene expression responses via PCR arrays involving 64 critical genes related to 10 different pathways. Our analysis showed that GPE peptidomimetics modulate oxidative stress, ACh depletion, α-secretase inactivation, apoptotic, and necrotic cell death. In vitro results suggested that treatments with novel GPE analogs might be promising therapeutic agents for treatment and/or or prevention of AD.

中文翻译：

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糖基-L-脯氨酰-L-谷氨酸假三肽治疗阿尔茨海默氏病

迄今为止，在临床实践中尚无有效的阿尔茨海默氏病（AD）缓解疾病的疗法。在这种情况下，甘氨酸-L-脯氨酸-L-谷氨酸（GPE）及其类似物可能为开发新型分子治疗神经退行性疾病（包括AD）开辟道路。反过来，本研究的目的是利用体外AD模型研究三种新型GPE拟肽（GPE1，GPE2和GPE3）发挥的神经保护作用。使用多种技术确定抗阿尔茨海默氏症的潜能，例如线粒体生存力（MTT）和乳酸脱氢酶（LDH）释放测定的测定，乙酰胆碱酯酶（AChE），α-分泌酶和β-分泌酶活性的测定，总和的比较抗氧化剂能力（TAC）和总氧化态（TOS）含量，流式细胞术和显微镜检测凋亡和坏死性神经元死亡，并通过涉及64个与10种不同途径相关的关键基因的PCR阵列研究基因表达反应。我们的分析表明，GPE拟肽能调节氧化应激，ACh耗竭，α-分泌酶失活，凋亡和坏死细胞死亡。体外结果表明，用新型GPE类似物进行治疗可能是用于治疗和/或预防AD的有前途的治疗剂。