Mushtaq Gohar, Greig Nigel H, Khan Jalaluddin A, Kamal Mohammad A
Department of Biochemistry, College of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
CNS Neurol Disord Drug Targets. 2014;13(8):1432-9. doi: 10.2174/1871527313666141023141545.
Both Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM) share the presence of systemic and neuro-inflammation, enhanced production and accumulation of β -amyloid peptide and abnormal levels of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Altered levels of AChE and BuChE both in AD as well as in T2DM imply that those two enzymes may be playing a pivotal role in the pathogenesis of the two disorders. AD and T2DM are both characterized by elevated levels of AChE and BuChE in the plasma. On the other hand, in AD the brain levels of AChE go down while those of BuChE go up, resulting in deregulation in balance between AChE and BuChE. This imbalance and change in the AChE/BuChE ratio causes cholinergic deficit in the brain, i.e. deficiency in the brain neurotransmitter acetylcholine. With better understanding of the inter-relationship of AChE and BuChE levels in normality as well as abnormality, AD and T2DM can be effectively treated. Thus, general cholinesterase inhibitors that inhibit both AChE and BuChE as well as highly selective BuChE inhibitors may have potential therapeutic benefits in the treatment of AD and other related dementias.
阿尔茨海默病（AD）和2型糖尿病（T2DM）都存在全身炎症和神经炎症，β-淀粉样肽的产生和积累增加，以及乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）水平异常。AD和T2DM中AChE和BuChE水平的改变表明，这两种酶可能在这两种疾病的发病机制中起关键作用。AD和T2DM的特征都是血浆中AChE和BuChE水平升高。另一方面，在AD中，大脑中AChE水平下降而BuChE水平上升，导致AChE和BuChE之间的平衡失调。这种AChE/BuChE比值的失衡和变化会导致大脑中的胆碱能缺陷，即大脑神经递质乙酰胆碱缺乏。随着对正常和异常情况下AChE和BuChE水平相互关系的更好理解，AD和T2DM可以得到有效治疗。因此，抑制AChE和BuChE的一般胆碱酯酶抑制剂以及高度选择性的BuChE抑制剂可能在治疗AD和其他相关痴呆症方面具有潜在的治疗益处。
