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.
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