Fu Ai Ling, Li Qian, Dong Zhao Hui, Huang Shi Jie, Wang Yu Xia, Sun Man Ji
Department of Biochemistry and Pharmacology, Institute of Pharmacology and Toxicology, Tai Ping Road, 27, 100850 Beijing, China.
Neurosci Lett. 2004 Sep 30;368(3):258-62. doi: 10.1016/j.neulet.2004.05.116.
Much evidence indicates that the memory and cognitive deficits of patients with Alzheimer's disease are closely associated with dysfunction of central cholinergic system. The degree of reduction of choline acetyltransferase activity in cerebral cholinergic neurons is significantly correlated with the severity of dementia or cognitive impairments observed in Alzheimer's disease. Therefore, Alzheimer's disease may be slowed by supplementation of exogenous choline acetyltransferase. Here we show that choline acetyltransferase mediated by TAT protein transduction domain passes through the blood-brain barrier and enters the neurons in mice, increasing choline acetyltransferase and neurotransmitter acetylcholine contents. The recombination TAT-choline acetyltransferase fusion protein injected intravenously improves the memory and cognitive dysfunction in Alzheimer's disease model mice induced by amyloid-beta peptide. Our results imply a novel and potentially effective way for Alzheimer's disease therapy.
大量证据表明，阿尔茨海默病患者的记忆和认知缺陷与中枢胆碱能系统功能障碍密切相关。大脑胆碱能神经元中胆碱乙酰转移酶活性的降低程度与阿尔茨海默病中观察到的痴呆或认知障碍的严重程度显著相关。因此，补充外源性胆碱乙酰转移酶可能会减缓阿尔茨海默病的发展。在此我们表明，由TAT蛋白转导结构域介导的胆碱乙酰转移酶穿过血脑屏障并进入小鼠神经元，增加胆碱乙酰转移酶和神经递质乙酰胆碱的含量。静脉注射重组TAT-胆碱乙酰转移酶融合蛋白可改善由β-淀粉样肽诱导的阿尔茨海默病模型小鼠的记忆和认知功能障碍。我们的结果暗示了一种治疗阿尔茨海默病的新的且可能有效的方法。
