机构:[a]Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, 100053, PR China检验科首都医科大学宣武医院[b]Beijing Institute of Brain Disorders, Capital Medical University, Beijing, 100053, PR China
Age-related changes such as increased oxidative stress and DNA damage are important risk factors for Alzheimer's disease (AD). This study aimed to clarify the role of POLD1, the catalytic subunit of DNA polymerase δ, in neurodegeneration symptoms of AD. POLD1 expression levels were evaluated in patients with different neurodegenerative diseases by ELISA, RT-PCR and Western blot analysis. The impairment of cognitive ability in AD patients and senescence-accelerated mouse prone 8 (SAMP8) mice were evaluated by MMSE/MoCA score and Morris water maze (MWM) test. We found that serum concentration and expression levels of POLD1 in lymphocytes were reduced in AD patients. The cognitive impairment in AD patients and SAMP8 mice was associated with reduced POLD1 expression. In addition, POLD1 knockdown led to premature senescence and increased DNA damage in primary neuronal cells of SAMP8 mice. In conclusion, this is the first study suggesting that the deficiency of POLD1 may aggravate AD progression, and POLD1 is a potential diagnostic marker and therapeutic target for AD. ? 2019 The Author
基金:
This work was supported by grants from the National Nature Science Foundation of China (No. 81271924 , 81472007 , 81871714 ) and Beijing Municipal Administration of Hospitals’ Ascent Plan (No. DFL20180803 ).
语种:
外文
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PubmedID:
中科院(CAS)分区:
出版当年[2018]版:
大类|3 区医学
小类|3 区医学:研究与实验3 区药学
最新[2023]版:
大类|2 区医学
小类|1 区药学2 区医学:研究与实验
JCR分区:
出版当年[2017]版:
Q2PHARMACOLOGY & PHARMACYQ2MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版:
Q1MEDICINE, RESEARCH & EXPERIMENTALQ1PHARMACOLOGY & PHARMACY
第一作者机构:[a]Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, 100053, PR China
通讯作者:
通讯机构:[a]Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, 100053, PR China
推荐引用方式(GB/T 7714):
Shichao Gao,Xiaomin Zhang,Qiao Song,et al.POLD1 deficiency is involved in cognitive function impairment in AD patients and SAMP8 mice[J].BIOMEDICINE & PHARMACOTHERAPY.2019,114:doi:10.1016/j.biopha.2019.108833.
APA:
Shichao Gao,Xiaomin Zhang,Qiao Song,Jing Liu,Xunming Ji&Peichang Wang.(2019).POLD1 deficiency is involved in cognitive function impairment in AD patients and SAMP8 mice.BIOMEDICINE & PHARMACOTHERAPY,114,
MLA:
Shichao Gao,et al."POLD1 deficiency is involved in cognitive function impairment in AD patients and SAMP8 mice".BIOMEDICINE & PHARMACOTHERAPY 114.(2019)