Research advances in the Wnt/β-catenin signaling pathway in neuronal degeneration in Alzheimer’s Disease
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    Abstract:

    Objective: Alzheimer’s disease (AD) is the most common type of dementia in the elderly, but its pathogenesis is complex and remains unclear. The most common neuropathological features of AD include amyloid β-protein (Aβ) deposition, neurofibrillary tangles due to hyperphosphorylation of Tau protein, and the activation of brain neuroinflammation, with neuronal injury and impaired learning and memory abilities. A growing number of studies have shown that the Wnt/β-catenin signaling pathway plays an important role in neurodegenerative disorders, especially in AD. This article reviews the related literature to clarify the association of the Wnt/β-catenin signaling pathway with the pathogenesis of AD, Aβ deposition, Tau protein, and neuroinflammation and related mechanism. Methods: The articles on the association of the Wnt/β-catenin signaling pathway with AD, Aβ neurotoxicity, Tau protein phosphorylation, and neuroinflammation, published in China and foreign countries, were reviewed. Results: Studies showed that the Wnt/β-catenin signaling pathway was involved in the development and progression of AD. The activation of this pathway inhibited Aβ deposition, hyperphosphorylation of Tau protein, and neuroinflammation, and on the contrary, it promoted the formation and aggregation of Aβ, the phosphorylation of Tau protein, and the development of neuroinflammation. Conclusion: This article reviews the importance of the Wnt/β-catenin signaling pathway in the pathogenesis of AD and provides a theoretical basis for the research on the pathogenesis of AD. It is pointed out that activation of the Wnt/β-catenin signaling pathway may be used as a potential target for the treatment of AD.patients,who were diagnosed with NSCLC in Sichuan Provincial People’s Hospital(as observation group),and 50 healthy people(as control group). Assay kits were used to determine the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and catalase(CAT) in plasma. The mRNA and protein expression of Klotho in plasma was measured/determined by qPCR and Western blot,respectively. Pearson correlation analysis was performed for the correlation between Klotho expression level and oxidative stress. Klotho methylation level was determined by methylation-specific PCR(MS-PCR). The methylation rate of CpG islands was determined by pyrosequencing. Results:Compared with the control group,the observation group had significantly reduced levels of SOD[(79.86±18.24) mU/L vs. (94.56±16.40) mU/L,t=4.487,P=0.000] and CAT[(18.50±4.62) U/mg vs. (25.26±3.54) U/mg,t=8.605,P=0.000],but there was no significant difference in MDA level between the observation group and the control group[(2.87±2.26) pg/mL vs. (2.52±1.06) pg/mL,t= 1.675,P=0.097]. The mRNA and protein expression levels of Klotho in plasma were significantly lower in the obser-vation group than in the control group(mRNA:0.66±0.16 vs. 1.04±0.10,t=14.93,P=0.000;protein:0.70±0.20 vs. 1.04±0.10,t=10.92,P= 0.000). There was a positive correlation between the protein expression of Klotho and the levels of SOD(r=0.768,P=0.000) and CAT(r=0.708,P=0.000). Meanwhile,the observation group had an increased methylation level of CpG islands in the Klotho promoter. Conclusion:Klotho methylation may be a clinical marker of oxidative stress in the plasma of patients with NSCLC.

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Xu Pengjuan, Cai Qing, Tan Junzhen, Chang Kaixuan, Chen Yilun, Fu Pengyu. Research advances in the Wnt/β-catenin signaling pathway in neuronal degeneration in Alzheimer’s Disease[J]. Journal of Chongqing Medical University,2019,(4):419-

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  • Online: April 22,2019
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