Melis ŞEN, Ulaş Ay, Erdem Tüzün, Cem İsmail Küçükali

Nörodejeneratif Hastalıklara DNA Onarım Mekanizmalarının Rolü

DNA stabil yapıda olmasına rağmen, endojen ve ekzojen kaynaklı ajanlar tarafından hasara uğramaolasılığı yüksek bir moleküldür. Eğer oluşan DNA hasarı onarılmazsa; hücrede apoptoz, yaşlanma gibiolumsuz durumlar oluşur ve DNA’da genomik mutasyonlar meydana gelebilir. Bu yüzden organizmalarkendilerine uygun birtakım DNA onarım mekanizmaları geliştirmiştir. Bu onarım mekanizmaları canlılığınbütünlüğü ve devamlılığı için oldukça önemlidir.DNA hasarları, nörodejeneratif hastalıkların patogenezinde rol alır. Nöronlarda postmitotik hücrelerolması nedeni ile daha çok baz kaybı mutasyonları ve DNA zincir kırıkları mutasyonları görülürken;mevcut oksijenin %20’sini kullanan beyinde ise oksidatif strese dayalı DNA hasarları oluşur. Ayrıcanörodejeneratif hastalığın varlığı DNA onarım mekanizmalarının işleyişini değiştirir.Bu derlemede DNA onarım mekanizmaları gözden geçirilecek ve Huntington Hastalığı, AlzheimerHastalığı, Parkinson Hastalığı, Amytrofik Lateral Skleroz Hastalığı, Friedreich Ataksisi, Ataksi Telanjiektazi,Herediter Spastik Parapleji Hastalıklarında DNA onarım mekanizmalarının rolünden bahsedilecektir.

Anahtar Kelimeler:

DNA onarımı mekanizmaları, nörodejeneratif hastalıklar, oksidatif stres, Huntington Hastalığı, Alzheimer Hastalığı, Parkinson Hastalığı, Amytrofik Lateral Skleroz Hastalığı, Friedreich Ataksisi, Ataksi Telanjiektazi, Herediter Spastik Parapleji

THE ROLE OF DNA REPAIR MECHANISMS IN NEURODEGENERATIVE DISEASES

Although DNA is stable, it is a molecule likely to be damaged by endogenous and exogenous sources.If the resulting DNA damage is not repaired; adverse events may occur in the cell such as apoptosisand aging, and genomic mutations in DNA. Therefore, organisms have developed a number ofDNA repair mechanisms that are appropriate for them. These repair mechanisms are very importantfor the integrity and continuity of life.DNA damage plays a role in the pathogenesis of neurodegenerative diseases. As neurons are postmitoticcells, mutations in base loss mutations and DNA chain breaks are more common, whereas thebrain uses 20% of the available oxygen, DNA damage occurs due to oxidative stress. Also thepresence of neurodegenerative disease changes the functioning of DNA repair mechanisms.This review will discuss DNA repair mechanisms and the role of DNA repair mechanisms in Huntington’sdisease, Alzheimer’s disease, Parkinson’s disease, Amytrophic Lateral Sclerosis, Friedreich’sAtaxia, Ataxia Telangiectasia and Hereditary Spastic Paraplegia.

Keywords:

DNA repair mechanisms, neurodegenerative diseases, oxidative stress, Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, Amytrophic Lateral Sclerosis, Friedreich’s Ataxia, Ataxia Telangiectasia, Hereditary Spastic Paraplegia,

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