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Research in Pharmaceutical Sciences، جلد ۱۸، شماره ۴، صفحات ۴۰۴-۴۱۲
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چکیده فارسی مقاله
کلیدواژه‌های فارسی مقاله
عنوان انگلیسی The effect of mutation on neurotoxicity reduction of new chimeric reteplase, a computational study
چکیده انگلیسی مقاله Background and purpose: Excitotoxicity in nerve cells is a type of neurotoxicity in which excessive stimulation of receptors (such as N-methyl-d-aspartate glutamate receptors (NMDAR)) leads to the influx of high-level calcium ions into cells and finally cell damage or death. This complication can occur after taking some of the plasminogen activators like tissue plasminogen activator and reteplase. The interaction of the kringle2 domain in such plasminogen activator with the amino-terminal domain (ATD) of the NR1 subunit of NMDAR finally leads to excitotoxicity. In this study, we assessed the interaction of two new chimeric reteplase, mutated in the kringle2 domain, with ATD and compared the interaction of wild-type reteplase with ATD, computationally. Experimental approach: Homology modeling, protein docking, molecular dynamic simulation, and molecular dynamics trajectory analysis were used for the assessment of this interaction. Findings/Results: The results of the free energy analysis between reteplase and ATD (wild reteplase: -2127.516 ± 0.0, M1-chr: -1761.510 ± 0.0, M2-chr: -521.908 ± 0.0) showed lower interaction of this chimeric reteplase with ATD compared to the wild type. Conclusion and implications: The decreased interaction between two chimeric reteplase and ATD of NR1 subunit in NMDAR which leads to lower neurotoxicity related to these drugs, can be the start of a way to conduct more tests and if the results confirm this feature, they can be considered potential drugs in acute ischemic stroke treatment. 
کلیدواژه‌های انگلیسی مقاله Chimeric reteplase,Docking,Molecular dynamic simulation,Excitotoxicity,Neurotoxicity.
نویسندگان مقاله | Pardis Mohammadi pour
Biology Department, Faculty of Science, Shahrekord University, Shahrekord, Iran.


| Karim Mahnam
Department of Anatomy and Cell Biology, McGill University, Montreal, H3A 0C7, QC, Canada.


| Mahsa Taherzadeh
Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.


| Shahrzad Ahangarzadeh
Molecular Medicine Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.


| Abbas Alibakhshi
Core Research Facilities, Isfahan University of Medical Sciences, Isfahan, Iran. Applied Physiology Research Center, Cardiovascular Research Institute, Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran.


| Elmira Mohammadi


نشانی اینترنتی http://rps.mui.ac.ir/index.php/jrps/article/view/2200
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زبان مقاله منتشر شده en
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نوع مقاله منتشر شده Original Article
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