Role of Acetylcholinesterase in β-Amyloid Aggregation Studied by Accelerated Molecular Dynamics

被引：30
作者：
Lushchekina S.V. [1 ,2 ]
Kots E.D. [1 ,3 ]
Novichkova D.A. [3 ]
Petrov K.A. [2 ,4 ]
Masson P. [4 ]
机构：
[1] N.M. Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, Kosygina Str., 4, Moscow
[2] A.E. Arbuzov Institute of Organic and Physical Chemistry of Russian Academy of Sciences, Arbuzov Str., 8, Kazan
[3] Chemistry Department, M.V. Lomonosov Moscow State University, Leninskie Gory, 1, Moscow
[4] Neuropharmacology Laboratory, Kazan Federal University, Kremlevskaia Str., 18, Kazan
来源：
BioNanoScience | 2017年 / 7卷 / 02期
基金：
俄罗斯科学基金会;
关键词：
Accelerated molecular dynamics; Acetylcholinesterase; β-amyloid;
D O I：
10.1007/s12668-016-0375-x
中图分类号：
学科分类号：
摘要：
Mechanisms of Alzheimer’s disease development are still under investigation. It was shown that acetylcholinesterase promotes aggregation of β-amyloid. Accelerated molecular dynamics simulations were performed to investigate molecular mechanisms of this process. Results showed that Aβ is strongly attracted to the surface of acetylcholinesterase and forms stable complexes. It was hypothesized that acetylcholinesterase serves as a nucleation center for propagation of β-amyloid aggregation. © 2016, Springer Science+Business Media New York.
引用
收藏
页码：396 / 402
页数：6
相关论文
共 26 条
[1]  
Agis-Torres A., Solhuber M., Fernandez M., Sanchez-Montero J.M., Multi-target-directed ligands and other therapeutic strategies in the search of a real solution for Alzheimer’s disease, Curr Neuropharmacol, 12, 1, pp. 2-36, (2014)
[2]  
Inestrosa N.C., Dinamarca M.C., Alvarez A., Amyloid–cholinesterase interactions, FEBS J, 275, 4, pp. 625-632, (2008)
[3]  
Semenov V.E., Zueva I.V., Mukhamedyarov M.A., Lushchekina S.V., Kharlamova A.D., Petukhova E.O., Mikhailov A.S., Podyachev S.N., Saifina L.F., Petrov K.A., Minnekhanova O.A., Zobov V.V., Nikolsky E.E., Masson P., Reznik V.S., 6-methyluracil derivatives as bifunctional acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease, ChemMedChem, 10, 11, pp. 1863-1874, (2015)
[4]  
De Ferrari G.V., Canales M.A., Shin I., Weiner L.M., Silman I., Inestrosa N.C., A structural motif of acetylcholinesterase that promotes amyloid β-peptide fibril formation, Biochemistry, 40, 35, pp. 10447-10457, (2001)
[5]  
Mishra P., Ayyannan S.R., Panda G., Perspectives on inhibiting beta-amyloid aggregation through structure-based drug design, ChemMedChem, 10, 9, pp. 1467-1474, (2015)
[6]  
Hou L.N., Xu J.R., Zhao Q.N., Gao X.L., Cui Y.Y., Xu J., Wang H., Chen H.Z., A new motif in the N-terminal of acetylcholinesterase triggers amyloid-beta aggregation and deposition, CNS neuroscience & therapeutics, 20, 1, pp. 59-66, (2014)
[7]  
Cheung J., Gary E.N., Shiomi K., Rosenberry T.L., Structures of human acetylcholinesterase bound to dihydrotanshinone I and territrem B show peripheral site flexibility, ACS Med Chem Lett, 4, 11, pp. 1091-1096, (2013)
[8]  
Kharlamova A.D., Lushchekina S.V., Petrov K.A., Kots E.D., Nachon F.V., Villard-Wandhammer M., Zueva I.V., Krejci E., Reznik V.S., Zobov V.V., Nikolsky E.E., Masson P., Slow-binding inhibition of acetylcholinesterase by an alkylammonium derivative of 6-methyluracil: mechanism and possible advantages for myasthenia gravis treatment, Biochem J, 473, 9, pp. 1225-1236, (2016)
[9]  
Crescenzi O., Tomaselli S., Guerrini R., Salvadori S., D'Ursi A.M., Temussi P.A., Picone D., Solution structure of the Alzheimer amyloid β-peptide (1–42) in an apolar microenvironment, Eur J Biochem, 269, 22, pp. 5642-5648, (2002)
[10]  
Humphrey W., Dalke A., Schulten K., VMD: visual molecular dynamics, J Mol Graph, 14, 1, pp. 33-38, (1996)
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