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POLD1 deficiency is involved in cognitive function impairment in AD patients and SAMP8 mice

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机构: [a]Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, 100053, PR China [b]Beijing Institute of Brain Disorders, Capital Medical University, Beijing, 100053, PR China
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关键词: Alzheimer's disease DNA damage repair POLD1 SAMP8

摘要:
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

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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
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出版当年[2017]版:
Q2 PHARMACOLOGY & PHARMACY Q2 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版] 出版后一年[2018版]

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第一作者机构: [a]Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, 100053, PR China
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通讯机构: [a]Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, 100053, PR China
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