近日，美国康奈尔大学Costantino Iadecola和Giuseppe Faraco等研究人员发现，食盐通过tau蛋白磷酸化促进认知障碍。这一研究成果2019年10月23日在线发表在国际学术期刊《自然》上。
研究人员发现，食盐诱导小鼠tau蛋白过度磷酸化，继而引起认知功能障碍，并且通过恢复内皮型一氧化氮的产生可以防止这些作用。一氧化氮缺乏会减少神经钙蛋白酶的亚硝化作用，并导致酶激活，进而通过激活细胞周期蛋白依赖性激酶5导致tau磷酸化。在tau蛋白缺失小鼠或接受过抗tau抗体治疗小鼠中未观察到盐引起的认知障碍，尽管持续存在脑灌注不足和神经血管功能障碍。
这些发现确定了食盐、内皮功能障碍和tau病理之间的因果关系，而与血流动力学不足无关。避免过量摄入盐和维持血管健康可能有助于避免老年痴呆症相关的血管和神经退行性病变。
据悉，饮食习惯和血管危险因素可促进阿尔茨海默症和由血管因素引起的认知障碍。此外，高磷酸化tau蛋白（一种微管相关蛋白）的积累和阿尔茨海默症的标志，也与血管性认知障碍有关。在小鼠中，高盐饮食会导致认知功能障碍，这与脑内皮细胞一氧化氮缺乏和脑灌注不足有关。
附：英文原文
Title: Dietary salt promotes cognitive impairment through tau phosphorylation
Author: Giuseppe Faraco, Karin Hochrainer, Steven G. Segarra, Samantha Schaeffer, Monica M. Santisteban, Ajay Menon, Hong Jiang, David M. Holtzman, Josef Anrather, Costantino Iadecola
Issue&Volume: 2019-10-23
Abstract: Dietary habits and vascular risk factors promote both Alzheimer’s disease and cognitive impairment caused by vascular factors1,2,3. Furthermore, accumulation of hyperphosphorylated tau, a microtubule-associated protein and a hallmark of Alzheimer’s pathology4, is also linked to vascular cognitive impairment5,6. In mice, a salt-rich diet leads to cognitive dysfunction associated with a nitric oxide deficit in cerebral endothelial cells and cerebral hypoperfusion7. Here we report that dietary salt induces hyperphosphorylation of tau followed by cognitive dysfunction in mice, and that these effects are prevented by restoring endothelial nitric oxide production. The nitric oxide deficiency reduces neuronal calpain nitrosylation and results in enzyme activation, which, in turn, leads to tau phosphorylation by activating cyclin-dependent kinase 5. Salt-induced cognitive impairment is not observed in tau-null mice or in mice treated with anti-tau antibodies, despite persistent cerebral hypoperfusion and neurovascular dysfunction. These findings identify a causal link between dietary salt, endothelial dysfunction and tau pathology, independent of haemodynamic insufficiency. Avoidance of excessive salt intake and maintenance of vascular health may help to stave off the vascular and neurodegenerative pathologies that underlie dementia in the elderly.
DOI: 10.1038/s41586-019-1688-z
Source: https://www.nature.com/articles/s41586-019-1688-z
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
