2012年11月5日 訊 /生物谷BIOON/ --易斯安那州立大學健康科學中心神經(jīng)科學教授Chu Chen博士領(lǐng)導的一項研究發(fā)現(xiàn)一種酶單酰基甘油脂肪酶（MAGL）可作為一種新的治療靶標來治療或預(yù)防老年癡呆癥,。相關(guān)研究發(fā)表于2012年11月1日的Cell雜志上,。
該研究小組發(fā)現(xiàn)，MAGL的失活能降低β-淀粉樣蛋白斑的產(chǎn)生和積累,，β-淀粉樣蛋白斑的積累是阿爾茨海默氏癥的主要病理特征,。抑制這種酶減少了神經(jīng)炎癥和神經(jīng)退行性疾病,，并能改善大腦的可塑性，促進學習和記憶,。
研究結(jié)果表明,，MAGL有助于引發(fā)阿爾茨海默氏癥，是一個很有潛力的治療靶點,，阻斷MAGL可以預(yù)防老年癡呆癥,。研究人員在小鼠中用高度選擇性的抑制劑阻斷MAGL，結(jié)果發(fā)現(xiàn) MAGL失活八周時間后是足以降低β-淀粉樣蛋白斑的沉積,，同時使得β淀粉樣蛋白對腦細胞產(chǎn)生毒性所涉及的基因功能也受到抑制,。
他們還測量了神經(jīng)炎癥和神經(jīng)退行性病變的指標，研究小組發(fā)現(xiàn)給予抑制劑治療的小鼠大腦中與認知相關(guān)的神經(jīng)突觸的結(jié)構(gòu)和功能完整性保持不變,，但MAGL失活卻能促進學習和記憶,。
阿爾茨海默氏癥是一種神經(jīng)退行性疾病，特點是淀粉樣蛋白斑塊的積累和沉積,，神經(jīng)原纖維纏結(jié),，患者認知功能逐漸惡化和喪失記憶。老年癡呆癥是老年人最常見的疾病之一,，這項研究得到了美國國立衛(wèi)生研究院的資助,。（生物谷：Bioon）
doi:10.1016/j.celrep.2012.09.030
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Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease.
Rongqing Chen, Jian Zhang, Yan Wu, Dongqing Wang, Guoping Feng, Ya-Ping Tang, Zhaoqian Teng, Chu Chen.
Alzheimer's disease (AD) is the most common cause of dementia among older people. There are no effective medications currently available to prevent and treat AD and halt disease progression. Monoacylglycerol lipase (MAGL) is the primary enzyme metabolizing the endocannabinoid 2-arachidonoylglycerol in the brain. We show here that inactivation of MAGL robustly suppressed production and accumulation of β-amyloid (Aβ) associated with reduced expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) in a mouse model of AD. MAGL inhibition also prevented neuroinflammation, decreased neurodegeneration, maintained integrity of hippocampal synaptic structure and function, and improved long-term synaptic plasticity, spatial learning, and memory in AD animals. Although the molecular mechanisms underlying the beneficial effects produced by MAGL inhibition remain to be determined, our results suggest that MAGL, which regulates endocannabinoid and prostaglandin signaling, contributes to pathogenesis and neuropathology of AD, and thus is a promising therapeutic target for the prevention and treatment of AD.
