復(fù)旦大學(xué)附屬中山醫(yī)院神經(jīng)內(nèi)科鐘春玖教授通過(guò)長(zhǎng)達(dá)10年潛心研究,，發(fā)現(xiàn)一種新型維生素B1衍生物能顯著改善老年性癡呆小鼠模型的認(rèn)知功能和病理?yè)p害,。
日前，國(guó)際著名學(xué)術(shù)雜志BRAIN發(fā)表了鐘春玖教授與中科院神經(jīng)科學(xué)研究所徐天樂(lè)研究員合作研究的成果,。這標(biāo)志著我國(guó)在防治老年性癡呆研究方面獲得新的突破,。
鐘春玖教授領(lǐng)銜的課題組利用老年性癡呆轉(zhuǎn)基因小鼠模型研究發(fā)現(xiàn)，一個(gè)新型維生素B1衍生物治療八周后,，能顯著增加老年性癡呆轉(zhuǎn)基因小鼠模型在Morris水迷宮第Ⅳ象限穿臺(tái)次數(shù)和停留時(shí)間,，減少癡呆小鼠腦內(nèi)老年斑和神經(jīng)纖維纏結(jié)數(shù)量，具有劑量?效應(yīng)關(guān)系,。鐘春玖教授領(lǐng)軍的課題組與中國(guó)科學(xué)院徐天樂(lè)研究員領(lǐng)軍的課題組合作的實(shí)驗(yàn)結(jié)果還表明,，該新型維生素B1衍生物是通過(guò)非維生素B1依賴的作用機(jī)制發(fā)揮作用的，其藥理作用與顯著增加糖合酶－3α和3β的磷酸化,，抑制糖合酶－3活性有關(guān),。（生物谷Bioon.com）
生物谷推薦原文出處：
Brain 2010 133(5):1342-1351; doi:10.1093/brain/awq069
Powerful beneficial effects of benfotiamine on cognitive impairment and β-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice
Xiaoli Pan1,*, Neng Gong2,*, Jing Zhao1, Zhe Yu2, Fenghua Gu3, Jia Chen3, Xiaojing Sun1, Lei Zhao1, Meijing Yu3, Zhiru Xu3, Wenxin Dong3, Yan Qin3, Guoqiang Fei1, Chunjiu Zhong1 and Tian-Le Xu2
1 Department of Neurology, Zhongshan Hospital & Shanghai Medical College, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China 2 Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China 3 Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China
Reduction of glucose metabolism in brain is one of the main features of Alzheimer’s disease. Thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer’s disease. However, thiamine treatment exerts little beneficial effect in these patients. Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer’s disease, the amyloid precursor protein/presenilin-1 transgenic mouse. We show that after a chronic 8 week treatment, benfotiamine dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test. Furthermore, benfotiamine effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains. Unexpectedly, these effects were not mimicked by another lipophilic thiamine derivative, fursultiamine, although both benfotiamine and fursultiamine were effective in increasing the levels of free thiamine in the brain. Most notably, benfotiamine, but not fursultiamine, significantly elevated the phosphorylation level of glycogen synthase kinase-3 and -3β, and reduced their enzymatic activities in the amyloid precursor protein/presenilin-1 transgenic brain. Therefore, in the animal Alzheimer’s disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities. These results suggest that, unlike many other thiamine-related drugs, benfotiamine may be beneficial for clinical Alzheimer’s disease treatment.
