Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Chem Biol Interact. 2010 Sep 6;187(1-3):425-31. doi: 10.1016/j.cbi.2010.01.037. Epub 2010 Feb 1.
Butyrylcholinesterase (BuChE) is an enzyme capable of hydrolysing a wide variety of esters including acetylcholine, a molecule involved in neurotransmission and modulation of immune cell activity. In the brain, BuChE is expressed in white matter and certain populations of neurons and glia. Multiple sclerosis (MS) is an autoimmune disease affecting white matter characterized by neuroinflammation and neurodegeneration in the central nervous system. Here we demonstrate alterations in BuChE activity in MS white matter lesions, including diminished enzyme activity associated with myelin and an increased activity in cells with microglial morphology. Increased BuChE activity within MS lesions could contribute to the pro-inflammatory immune responses through hydrolysis of acetylcholine and to demyelination through hydrolytic deacylation of myelin proteins such as proteolipid protein. This suggests that BuChE could be a potential target for novel disease-modifying strategies for MS.
丁酰胆碱酯酶(BuChE)是一种能够水解多种酯类的酶,包括参与神经递质传递和免疫细胞活性调节的乙酰胆碱。在大脑中,BuChE 表达于白质和某些神经元和神经胶质细胞群体中。多发性硬化症(MS)是一种自身免疫性疾病,影响白质,其特征是中枢神经系统的神经炎症和神经退行性变。在这里,我们证明了 MS 白质病变中 BuChE 活性的改变,包括与髓鞘相关的酶活性降低和具有小胶质细胞形态的细胞中活性增加。MS 病变中 BuChE 活性的增加可能通过水解乙酰胆碱导致促炎免疫反应,并通过水解髓鞘蛋白如蛋白脂质蛋白进行脱酰基化导致脱髓鞘。这表明 BuChE 可能是 MS 新型疾病修饰治疗策略的潜在靶点。