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首页> 外文期刊>CNS drug reviews >NAP: research and development of a peptide derived from activity-dependent neuroprotective protein (ADNP).
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NAP: research and development of a peptide derived from activity-dependent neuroprotective protein (ADNP).

机译：NAP：研究和开发源自活性依赖性神经保护蛋白（ADNP）的肽。

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Activity-dependent neuroprotective protein (ADNP) is essential for brain formation. Peptide activity scanning identified NAP (NAPVSIPQ) as a small active fragment of ADNP that provides neuroprotection at very low concentrations. In cell culture, NAP has demonstrated protection against toxicity associated with the beta-amyloid peptide, N-methyl-D-aspartate, electrical blockade, the envelope protein of the AIDS virus, dopamine, H2O2, nutrient starvation and zinc overload. NAP has also provided neuroprotection in animal models of apolipoprotein E deficiency, cholinergic toxicity, closed head injury, stroke, middle aged anxiety and cognitive dysfunction. NAP binds to tubulin and facilitates microtubule assembly leading to enhanced cellular survival that is associated with fundamental cytoskeletal elements. A liquid-chromatography, mass spectrometry assay demonstrated that NAP reaches the brain after either intravenous or intranasal administration. In a battery of toxicological tests including repeated dose toxicity in rats and dogs, cardiopulmonary tests in dogs, and functional behavioral assays in rats, no adverse side effects were observed with NAP concentrations that were approximately 500-fold higher than the biologically active dose. A Phase Ia clinical trial in the US assessed the tolerability and pharmacokinetics of intranasal administration of NAP in sequential ascending doses. The results supported the safety and tolerability of a single dose of NAP administered at up to 15 mg intranasally. Furthermore, dosing was recently completed for a second Phase I clinical trial in healthy adults and elderly volunteers with an intravenous formulation of NAP. NAP is poised for further clinical development targeting several indications, including Alzheimer's disease.
机译：依赖于活动的神经保护蛋白（ADNP）对于大脑形成至关重要。肽活性扫描将NAP（NAPVSIPQ）鉴定为ADNP的小活性片段，可在非常低的浓度下提供神经保护。在细胞培养中，NAP已显示出针对与β-淀粉样肽，N-甲基-D-天门冬氨酸，电封锁，艾滋病病毒的包膜蛋白，多巴胺，H2O2，营养缺乏和锌超载相关的毒性的保护作用。 NAP还为载脂蛋白E缺乏症，胆碱能毒性，闭合性颅脑损伤，中风，中年焦虑症和认知功能障碍的动物模型提供了神经保护作用。 NAP结合微管蛋白并促进微管组装，从而导致与基本细胞骨架成分相关的细胞存活率提高。液相色谱质谱分析表明，NAP在静脉内或鼻内给药后到达大脑。在一系列毒理学测试中，包括对大鼠和狗进行重复剂量毒性试验，对狗进行心肺试验以及对大鼠进行功能行​​为试验，发现NAP浓度比生物活性剂量高约500倍时，没有观察到不良副作用。在美国的Ia期临床试验评估了鼻内NAP连续递增剂量的耐受性和药代动力学。结果支持鼻内给予最高剂量为15 mg的单剂量NAP的安全性和耐受性。此外，最近通过静脉注射NAP在健康成人和老年志愿者中完成了第二期I期临床试验的剂量。 NAP准备针对包括阿尔茨海默氏病在内的多种适应症进行进一步的临床开发。

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