Parkinson Hastalığı ile İlişkilendirilen PreNAC Fibril Kesiti ve Onun A53C, A53E, A53G, A53T, A53V Mutasyonlarının Yapısal Kararlılığın Araştırılması

Year 2021, Volume: 16 Issue: 1, 66 - 76, 27.05.2021

Hakan Alıcı Kadir Demir

https://doi.org/10.29233/sdufeffd.824140

Abstract

Parkinson hastalığının (PD) başlıca patolojik işaretlerinden biri beyinde kümelenmiş alfa-sinüklein agregalarının oluşturdukları fibril yapılardır. Bu çalışmada PreNAC olarak adlandırılan bir alfa-sinüklein fibril kesiti ve onun 53. aminoasidinin A53C, A53E, A53G, A53T ve A53V mutasyon fibril yapıları üzerine odaklanılmıştır. Ele alınan tüm fibril kesiti sistemlerinin yapısal kararlılıkları ve yaprak tabakları arasındaki etkileşimler Moleküler Dinamik (MD) simülasyon yöntemi kullanılarak incelenmiştir. Böylece ilgilenilen fibril kesitlerinin gelecekteki muhtemel ilaç geliştirme çalışmaları için hedef yapı olabilme ihtimalleri değerlendirilmiştir. Çalışmada elde edilen bulgulara göre, vahşi tip fibril kesiti ve onun kalıtsal mutasyonlarını içeren A53E, A53T, A53V fibril kesitlerinin simülasyonlar boyunca önemli ölçüde konformasyonel formlarını kararlı bir şekilde koruduğu gözlemlenirken öte yandan A53G mutasyonunun fibril kesitini dağıtıcı bir etki gösterdiği tespit edilmiştir.

Keywords

PreNAC, Moleküler Dinamik, Simülasyon, Parkinson Hastalığı

Supporting Institution

Zonguldak Bülent Ecevit Üniversitesi

Project Number

2015-22794455-03

Thanks

Bu çalışmaya 2015-22794455-03 nolu Altyapı Projesi ile kaynak sağlayan Zonguldak Bülent Ecevit Üniversitesi Bilimsel Araştırmalar Proje Birimi’ne teşekkür ederiz.

Investigation of the Structural Stability of PreNAC and its A53C, A53E, A53G, A53T, A53V Mutant Fibril Segments Associated with Parkinson's Disease

Abstract

A pathological hallmark of Parkinson's disease (PD) is the fibrillar structures formed by alpha-synuclein aggregates accumulated in the brain. In this study, we focused on an alpha-synuclein PreNAC fibril segment and it’s A53C, A53E, A53G, A53T and A53V mutations. The structural stability and the interactions between sheets of all fibril systems studied in this paper were examined using the Molecular Dynamic (MD) simulation method and thus the possibilities of these fibril segments to be target structures for future drug development efforts was evaluated. According to the findings obtained from our MD simulations, it was determined that the wild type (WT) fibril segment and its A53E, A53T and A53V fibril structures with hereditary mutations preserved significantly their stable conformational structure along the simulations, whereas the A53G mutation had a disruptive effect on the fibril segment.

Keywords

PreNAC, Molecular Dynamics, Simulation, Parkinson’s disease

Project Number

2015-22794455-03

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