Department of Pharmacology, Oxford University, Mansfield Rd, Oxford OX1 3QT, United Kingdom.
Chem Biol Interact. 2010 Sep 6;187(1-3):110-4. doi: 10.1016/j.cbi.2010.02.010. Epub 2010 Feb 13.
A novel theory for neurodegeneration is that non-cholinergic functions of acetylcholinesterase (AChE) are responsible for the progressive death of global neurons. The C-terminal region of AChE has been shown to be responsible for non-cholinergic actions of AChE by binding to an allosteric site on the alpha 7-nicotinic acetylcholine receptor, thereby causing calcium influx; the resultant signal has trophic effects in immature neurons, but toxic effects in mature neurons. Although there is strong in vitro and in vivo evidence for the involvement of this C-terminal region of AChE in neurodegeneration, a cleaved C-terminal peptide has not yet been identified in human brains. This preliminary study aimed to identify the cleaved AChE C-terminal peptide in serum from human Alzheimer's disease patients using immunoaffinity purification. A number of antibodies were tested for sensitivity and specificity towards peptide sequences from the C-terminus. Although the antibodies were able to identify peptide in vitro, peptide was not detected using immunoaffinity purification of human serum, possibly due to insufficient detection limits of the antibody. Therefore more sensitive techniques are required to identify cleaved AChE C-terminal peptides in human samples. None the less, C-terminal AChE peptide might act as a signalling molecule in an as yet unexplored system.
一种新的神经退行性疾病理论认为，乙酰胆碱酯酶（AChE）的非胆碱能功能负责全球神经元的进行性死亡。AChE 的 C 末端区域通过与α7-烟碱型乙酰胆碱受体上的变构位点结合而负责 AChE 的非胆碱能作用，从而导致钙内流；由此产生的信号在未成熟神经元中有营养作用，但在成熟神经元中有毒性作用。尽管有强有力的体外和体内证据表明 AChE 的这个 C 末端区域参与神经退行性变，但尚未在人类大脑中鉴定出裂解的 C 末端肽。这项初步研究旨在使用免疫亲和纯化从人类阿尔茨海默病患者的血清中鉴定裂解的 AChE C 末端肽。测试了许多针对 C 末端肽序列的抗体的灵敏度和特异性。尽管抗体能够在体外识别肽，但使用免疫亲和纯化未能检测到人类血清中的肽，可能是由于抗体的检测限不足。因此，需要更敏感的技术来鉴定人类样本中的裂解 AChE C 末端肽。尽管如此，C 末端 AChE 肽可能在一个尚未探索的系统中作为信号分子发挥作用。
