Jung, Eun Sun Choi, Hyunjung Song, Hyundong Hwang, Yu Jin Kim, Ahbin Ryu, Hoon Mook-Jung, Inhee 2024-01-20T04:04:42Z 2024-01-20T04:04:42Z 2022-01-25 2016-05 2045-2322 https://pubs.kist.re.kr/handle/201004/124095 Alzheimer's disease (AD) is the most common type of dementia and age-related neurodegenerative disease. Elucidating the cellular changes that occur during ageing is an important step towards understanding the pathogenesis and progression of neurodegenerative disorders. SIRT6 is a member of the mammalian sirtuin family of anti-aging genes. However, the relationship between SIRT6 and AD has not yet been elucidated. Here, we report that SIRT6 protein expression levels are reduced in the brains of both the 5XFAD AD mouse model and AD patients. A beta 42, a major component of senile plaques, decreases SIRT6 expression, and A beta 42-induced DNA damage is prevented by the overexpression of SIRT6 in HT22 mouse hippocampal neurons. Also, there is a strong negative correlation between A beta 42-induced DNA damage and p53 levels, a protein involved in DNA repair and apoptosis. In addition, upregulation of p53 protein by Nutlin-3 prevents SIRT6 reduction and DNA damage induced by A beta 42. Taken together, this study reveals that p53-dependent SIRT6 expression protects cells from A beta 42-induced DNA damage, making SIRT6 a promising new therapeutic target for the treatment of AD. English NATURE PUBLISHING GROUP p53-dependent SIRT6 expression protects A beta 42-induced DNA damage Article 10.1038/srep25628 1 SCIENTIFIC REPORTS, v.6 SCIENTIFIC REPORTS 6 N scie scopus 000375441600001 2-s2.0-84969848895 Multidisciplinary Sciences Science & Technology - Other Topics Article N-TERMINAL-KINASE MILD COGNITIVE IMPAIRMENT ALZHEIMERS-DISEASE BRAIN BASE EXCISION-REPAIR GENOMIC INSTABILITY HISTONE DEACETYLASE NEURONAL APOPTOSIS MOUSE CELLS IN-VIVO P53