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褪黑素增强老年和阿尔茨海默病患者皮肤成纤维细胞中核心转录因子的表达。

Melatonin Augments the Expression of Core Transcription Factors in Aged and Alzheimer's Patient Skin Fibroblasts.

作者信息

Shukla Mayuri, Duangrat Raphiporn, Nopparat Chutikorn, Sotthibundhu Areechun, Govitrapong Piyarat

机构信息

Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Kamphaeng Phet 6, Bangkok 10210, Thailand.

Innovative Learning Center, Srinakharinwirot University, Sukhumvit 23, Bangkok 10110, Thailand.

出版信息

Biology (Basel). 2024 Sep 5;13(9):698. doi: 10.3390/biology13090698.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Altered neurogenesis and the appearance of AD pathological hallmarks are fundamental to this disease. SRY-Box transcription factor 2 (Sox2), octamer-binding transcription factor 4 (Oct4), and Nanog are a set of core transcription factors that play a very decisive role in the preservation of pluripotency and the self-renewal capacity of embryonic and adult stem cells. These factors are critically involved in AD pathogenesis, senescence, and aging. Skin fibroblasts are emblematic of cellular damage in patients. We, therefore, in the present study, analyzed the basal expression of these factors in young, aged, and AD fibroblasts. AD fibroblasts displayed an altered expression of these factors, differing from aged and young fibroblasts. Since melatonin is well acknowledged for its anti-aging, anti-senescence and anti-AD therapeutic benefits, we further investigated the effects of melatonin treatment on the expression of these factors in fibroblasts, along with precise validation of the observed data in human neuroblastoma SH-SY5Y cells. Our findings reveal that melatonin administration augmented the expression levels of Sox2, Oct4, and Nanog significantly in both cells. Altogether, our study presents the neuroprotective potential and efficacy of melatonin, which might have significant therapeutic benefits for aging and AD patients.

摘要

阿尔茨海默病(AD)是一种进行性神经退行性疾病。神经发生改变和AD病理特征的出现是这种疾病的基础。SRY盒转录因子2(Sox2)、八聚体结合转录因子4(Oct4)和Nanog是一组核心转录因子,它们在维持胚胎和成年干细胞的多能性和自我更新能力方面起着非常决定性的作用。这些因子与AD的发病机制、衰老密切相关。皮肤成纤维细胞是患者细胞损伤的标志。因此,在本研究中,我们分析了这些因子在年轻、老年和AD成纤维细胞中的基础表达。AD成纤维细胞显示出这些因子的表达改变,与老年和年轻成纤维细胞不同。由于褪黑素因其抗衰老、抗衰老和抗AD治疗益处而广为人知,我们进一步研究了褪黑素处理对成纤维细胞中这些因子表达的影响,并在人神经母细胞瘤SH-SY5Y细胞中对观察到的数据进行了精确验证。我们的研究结果表明,褪黑素处理显著提高了两种细胞中Sox2、Oct4和Nanog的表达水平。总之,我们的研究展示了褪黑素的神经保护潜力和功效,这可能对衰老和AD患者具有显著的治疗益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddd/11428320/f0cd0b2134e3/biology-13-00698-g001.jpg

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