Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5500626 | Ageing Research Reviews | 2017 | 14 Pages |
Abstract
In this review we will discuss the links between autophagy, a mechanism involved in the maintenance of cellular homeostasis and controlling cellular waste management, and the DNA damage response (DDR), comprising various mechanisms preserving the integrity and stability of the genome. A reduced autophagy capacity in retinal pigment epithelium has been shown to be connected in the pathogenesis of age-related macular degeneration (AMD), an eye disease. This degenerative disease is a major and increasing cause of vision loss in the elderly in developed countries, primarily due to the profound accumulation of intra- and extracellular waste: lipofuscin and drusen. An abundance of reactive oxygen species is produced in the retina since this tissue has a high oxygen demand and contains mitochondria-rich cells. The retina is exposed to light and it also houses many photoactive molecules. These factors are clearly reflected in both the autophagy and DNA damage rates, and in both nuclear and mitochondrial genomes. It remains to be revealed whether DNA damage and DDR capacity have a more direct role in the development of AMD.
Keywords
RPAmTORNHEJHDACAMDTSCSSBBERHspNrf2BRCAA2EmTORC1RPEsirtuin 1ATGFOXO3PARPATRSirt1AMPKPI3KDSBPCNA9-1-1 complexHRRATR interacting proteinDNA-PKcsDDRAMP-activated protein kinaseataxia telangiectasia and Rad3 relatedataxia-telangiectasia mutatedMitochondrial DNANERULKROSSQSTM1/p62proliferation cell nuclear antigenAutophagyretinal pigment epitheliumcheckpoint kinasenucleotide excision repairbase excision repairreplication protein AATMAge related macular degenerationmtDNASODATRIPage-related macular degenerationSuperoxide dismutaseAll-trans retinaldouble strand breaksingle strand breakNuclear factor-erythroid 2-related factor 2non-homologous end-joiningVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)phosphatidylinositol-3 kinaseMRN complexmammalian target of rapamycinMammalian target of rapamycin complex 1histone deacetylaseDNA damage responseHeat shock proteinmicrotubule-associated protein 1 light chain 3poly (ADP-ribose) polymeraseChkautophagy-related geneTuberous sclerosis complexReactive oxygen speciesUbiquitin
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Ageing
Authors
Juha M.T. Hyttinen, Janusz BÅasiak, Minna Niittykoski, Kati Kinnunen, Anu Kauppinen, Antero Salminen, Kai Kaarniranta,