title: Transcriptional mutagenesis by 8-oxodG in α-synuclein aggregation and the pathogenesis of Parkinson's disease.
abstract: Parkinson's disease (PD) is an age-related progressive neurodegenerative disease associated with selective loss of dopaminergic neurons. The characteristic hallmark of the disease is intracytoplasmic proteinacious inclusion bodies called Lewy bodies, primarily consisting of a presynaptic protein α-synuclein. Oxidative stress-mediated damage to macromolecules have been shown to occur frequently in PD. Oxidative damage to DNA in the form of oxidized guanine (8-oxodG) accumulates in both the mitochondrial and nuclear DNA of dopaminergic neurons of the substantia nigra in PD. 8-oxodG-mediated transcriptional mutagenesis has been shown to have the potential to alter phenotype of cells through production of mutant pool of proteins. This review comprehensively summarizes the role of oxidative stress-mediated damage incurred during neurodegeneration, and highlights the scope of transcriptional mutagenesis event in leading to α-synuclein aggregation as seen in PD.
authors: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA.
authors: Sambuddha
authors: S
authors: Basu
authors: Department of Biochemistry, College of Medicine, Kyung-Hee University, Seoul, Korea.
authors: Goun
authors: G
authors: Je
authors: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA.|Department of Biochemistry, College of Medicine, Kyung-Hee University, Seoul, Korea.
authors: Yoon-Seong
authors: YS
authors: Kim
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000595:Amino Acid Sequence; D000818:Animals; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D066263:Protein Aggregation, Pathological / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*; D014158:Transcription, Genetic; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine