MTH1 and OGG1 maintain a low level of 8-oxoguanine in Alzheimer's brain, and prevent the progression of Alzheimer's pathogenesis
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ABSTRACT: To investigate the role of 8-oxo-7, 8-dihydroguanine (8-oxoguanine) accumulation in DNA or nucleotide pools during the development of AD pathology, we introduced a Mth1/Ogg1-double deficiency into homozygous triple-transgenic AD model (3xTg-AD-H) mice. Mth1 encodes 8-oxo-7, 8-dihydro-2'-deoxyguanosine-5'-triphosphatase (8-oxo-dGTPase) and Ogg1 encodes 8-oxoguanine DNA glycosylase 1. One-way eBays ANOVA of microarray data from hippocampi revealed that the gene expression profiles are most significantly altered in the hippocampi of 3xTg-AD-H with Mth1/Ogg1-double deficient (ADH/TO-DKH) mice compared to non-Tg control (NT) mice. Comparative analysis between 3xTg-AD-H (ADH/WT) and ADH/TO-DKH mice showed that the expression of genes involved in neuroprotection are significantly altered. Among them, expression of the AD-related genes including Ttr, Enpp2, Kcnj13 and Kl was significantly downregulated in ADH/TO-DKH mice.
ORGANISM(S): Mus musculus
PROVIDER: GSE83996 | GEO | 2021/03/24
REPOSITORIES: GEO
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