EXPRESSION OF DNA EXCISION-REPAIR-CROSS-COMPLEMENTING PROTEINS P80 AND P89 IN BRAIN OF PATIENTS WITH DOWN-SYNDROME AND ALZHEIMERS-DISEASE

Although deficient DNA repair was proposed for neurodegenerative disor ders including Down syndrome (DS), repair proteins for nucleotide exci sion repair have not been studied in brain yet. As one of the hypothes es for the pathogenesis of brain damage in DS and Alzheimer's disease (AD), is oxidative stress, and cells of patients with DS were shown to be more susceptible to ionizing irradiation. We decided to study expr ession of excision repair-cross-complementing (ERCC) gene products, pr oteins 80 and 89, representatives of repair genes known to be involved in the repair of different types of DNA damage. ERCC2-protein 80 kDa and ERCC3-protein p89 were determined in five individual brain regions of controls, aged DS and AD patients. Although different in the indiv idual regions, DNA repair proteins were consistently higher in tempora l and frontal lobes of patients with DS and higher in all brain region s of patients with AD. Our results are the first to describe DNA repai r gene protein patterns in human brain regions providing the basis for further studies in this area. We showed that DNA repair genes ERCC2 a nd ERCC3 (excision-repair-cross-complementing) for nucleotide excision repair were increased at the protein level with the possible biologic al meaning that this increase may be compatible with and indicate ongo ing (oxidative?) DNA damage. (C) 1998 Elsevier Science Ireland Ltd. Al l rights reserved.