title: The role of DNA base excision repair in brain homeostasis and disease.
abstract: Chemical modification and spontaneous loss of nucleotide bases from DNA are estimated to occur at the rate of thousands per human cell per day. DNA base excision repair (BER) is a critical mechanism for repairing such lesions in nuclear and mitochondrial DNA. Defective expression or function of proteins required for BER or proteins that regulate BER have been consistently associated with neurological dysfunction and disease in humans. Recent studies suggest that DNA lesions in the nuclear and mitochondrial compartments and the cellular response to those lesions have a profound effect on cellular energy homeostasis, mitochondrial function and cellular bioenergetics, with especially strong influence on neurological function. Further studies in this area could lead to novel approaches to prevent and treat human neurodegenerative disease.
authors.affiliation: Center for Healthy Aging, SUND, University of Copenhagen, Denmark.
authors.forename: Mansour
authors.initials: M
authors.lastname: Akbari
authors.affiliation: Center for Healthy Aging, SUND, University of Copenhagen, Denmark.
authors.forename: Marya
authors.initials: M
authors.lastname: Morevati
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Baltimore, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Croteau
authors.affiliation: Center for Healthy Aging, SUND, University of Copenhagen, Denmark; Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Baltimore, USA. Electronic address: vbohr@nih.gov.
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins
chemical_list: D004272:DNA, Mitochondrial; D000075223:Poly-ADP-Ribose Binding Proteins; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C530380:PNKP protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes
keywords: Base excision repair; Mitochondrial DNA; Neurodegeneration; Oxidative damage; PARP-1