阿尔茨海默病中的淀粉样蛋白

阿尔茨海默病（Alzheimer’s disease, AD）是一种以老年人高发、伴有严重认知障碍的神经退行性疾病。淀粉样蛋白（amyloid β, Aβ）是在AD患者脑中发现的主要病理分子，其在AD发生发展中扮演着重要的角色，据此提出的淀粉样蛋白级联假说受到学界广泛认可。但目前针对以Aβ为靶点的治疗手段屡次失利，表明淀粉样蛋白级联假说已不足以全面描述AD的症状及发病机制，需要重新审视Aβ在疾病中的作用。本文综述淀粉样蛋白级联假说的提出及其发展、Aβ在AD中的作用和靶向Aβ的治疗效果，以期全面认识Aβ，为AD治疗提供新的思路。     

化学和物理干预治疗阿尔茨海默病的机制

阿尔茨海默病（Alzheimers’ disease, AD）是一种常见的以进行性认知障碍和记忆减退为主要特征的中枢神经退行性疾病，发病人数多，波及范围广，已成为老年医学中最严峻的问题之一。临床上AD的药物治疗效果有限，且存在一定的局限性与副作用。目前，物理干预AD的治疗方法正逐渐受到人们的关注和重视，研究表明，物理干预如嗅觉干预、光疗法、脑电刺激、声光刺激、温度干预等能通过提高神经发生、神经保护、调控神经元兴奋性和可塑性、提高脑血流量、改善代谢、减少Aβ沉积和Tau蛋白过度磷酸化等，从而改善AD症状与认知功能。本文综述了不同物理干预对AD的作用机制以及疗效，为物理干预用于实施预防和延缓AD提供理论基础。     

综述与专论：表观遗传修饰调控阿尔茨海默病的研究进展

阿尔茨海默病（Alzheimer’s disease,AD）是一种临床上常见的以进行性认知功能障碍和记忆减退为主要特征的神经退行性疾病。近些年研究发现，表观遗传修饰如DNA修饰、组蛋白修饰、RNA修饰及非编码RNA在Aβ沉积、Tau蛋白过度磷酸化、神经再生、突触可塑性和认知功能中发挥不同程度的调控作用，进而改善或加剧AD病理进程。临床数据表明表观遗传修饰的改变与AD风险呈显著相关性，运用药物、物理刺激、si RNA等干预手段在AD动物模型中改变表观遗传修饰水平可改善AD病理和认知能力。本文综述了不同的表观遗传修饰在AD中的调控作用，为进一步理解AD的表观遗传学机制及通过干预表观遗传修饰改善或治疗AD的可行性提供理论依据。     

LncRNA lnc-ISG20 promotes renal fibrosis in diabetic nephropathy by inducing AKT phosphorylation through miR-486-5p/NFAT5

Long non-coding RNA (lncRNA) lnc-ISG20 has been found aberrantly up-regulated in the glomerular in the patients with diabetic nephropathy (DN). We aimed to elucidate the function and regulatory mechanism of lncRNA lnc-ISG20 on DN-induced renal fibrosis. Expression patterns of lnc-ISG20 in kidney tissues of DN patients were determined by RT-qPCR. Mouse models of DN were constructed, while MCs were cultured under normal glucose (NG)/high glucose (HG) conditions. The expression patterns of fibrosis marker proteins collagen IV, fibronectin and TGF-β1 were measured with Western blot assay. In addition, the relationship among lnc-ISG20, miR-486-5p, NFAT5 and AKT were analysed using dual-luciferase reporter assay and RNA immunoprecipitation. The effect of lnc-ISG20 and miR-486/NFAT5/p-AKT axis on DN-associated renal fibrosis was also verified by means of rescue experiments. The expression levels of lnc-ISG20 were increased in DN patients, DN mouse kidney tissues and HG-treated MCs. Lnc-ISG20 silencing alleviated HG-induced fibrosis in MCs and delayed renal fibrosis in DN mice. Mechanistically, miR-486-5p was found to be a downstream miRNA of lnc-ISG20, while miR-486-5p inhibited the expression of NFAT5 by binding to its 3'UTR. NFAT5 overexpression aggravated HG-induced fibrosis by stimulating AKT phosphorylation. However, NFAT5 silencing reversed the promotion of in vitro and in vivo fibrosis caused by lnc-ISG20 overexpression. Our collective findings indicate that lnc-ISG20 promotes the renal fibrosis process in DN by activating AKT through the miR-486-5p/NFAT5 axis. High-expression levels of lnc-ISG20 may be a useful indicator for DN.