Exp Mol Med.  2015 Aug;47(8):e179. 10.1038/emm.2015.54.

Transcriptional mutagenesis by 8-oxodG in alpha-synuclein aggregation and the pathogenesis of Parkinson's disease

• Basu S
• Je G
• Kim YS

• KMID: 2155433
• DOI: http://doi.org/10.1038/emm.2015.54

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 alpha-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 alpha-synuclein aggregation as seen in PD.

MeSH Terms

Amino Acid Sequence
Animals
Deoxyguanosine/*analogs & derivatives/metabolism
Humans
Molecular Sequence Data
Mutagenesis
*Oxidative Stress
Parkinson Disease/*genetics/metabolism/pathology
Protein Aggregation, Pathological/*genetics/metabolism/pathology
Substantia Nigra/metabolism/*pathology
Transcription, Genetic
alpha-Synuclein/chemistry/*genetics
Deoxyguanosine
alpha-Synuclein