Nörodejeneratif Hastalıklara DNA Onarım Mekanizmalarının Rolü

Yıl 2017, Cilt: 7 Sayı: 13, 47 - 58, 01.06.2017

Melis Şen Ulaş Ay Erdem Tüzün , Cem İsmail Küçükali

Öz

DNA stabil yapıda olmasına rağmen, endojen ve ekzojen kaynaklı ajanlar tarafından hasara uğrama

olasılığı yüksek bir moleküldür. Eğer oluşan DNA hasarı onarılmazsa; hücrede apoptoz, yaşlanma gibi

olumsuz durumlar oluşur ve DNA’da genomik mutasyonlar meydana gelebilir. Bu yüzden organizmalar

kendilerine uygun birtakım DNA onarım mekanizmaları geliştirmiştir. Bu onarım mekanizmaları canlılığın

bütünlüğü ve devamlılığı için oldukça önemlidir.

DNA hasarları, nörodejeneratif hastalıkların patogenezinde rol alır. Nöronlarda postmitotik hücreler

olması 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. Ayrıca

nörodejeneratif hastalığın varlığı DNA onarım mekanizmalarının işleyişini değiştirir.

Bu derlemede DNA onarım mekanizmaları gözden geçirilecek ve Huntington Hastalığı, Alzheimer

Hastalığı, 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

Öz

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 apoptosis

and aging, and genomic mutations in DNA. Therefore, organisms have developed a number of

DNA repair mechanisms that are appropriate for them. These repair mechanisms are very important

for the integrity and continuity of life.

DNA damage plays a role in the pathogenesis of neurodegenerative diseases. As neurons are postmitotic

cells, mutations in base loss mutations and DNA chain breaks are more common, whereas the

brain uses 20% of the available oxygen, DNA damage occurs due to oxidative stress. Also the

presence 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’s

disease, Alzheimer’s disease, Parkinson’s disease, Amytrophic Lateral Sclerosis, Friedreich’s

Ataxia, Ataxia Telangiectasia and Hereditary Spastic Paraplegia.

Anahtar Kelimeler

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

Kaynakça

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