Department of Neurology, Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, PR China.
Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Aging (Albany NY). 2021 Aug 30;13(16):20716-20737. doi: 10.18632/aging.203457.
N6 adenosine methylation (m6A) is the most abundant internal RNA modification in eukaryotic cells. Dysregulation of m6A has been associated with the perturbations of cell proliferation and cell death in different diseases. However, the roles of m6A in the neurodegenerative process and cognitive dysfunction are unclear.
We systematically investigated the molecular alterations of m6A regulators and their clinical relevance with cognitive dysfunctions using published datasets of Alzheimer's Disease (AD), vascular dementia, and mild cognitive impairment (MCI).
The expressions of m6A regulators vary in different tissues and closely correlate with neurodegenerative pathways. We identified co-expressive m6A regulators SNRPG and SNRPD2 as potential biomarkers to predict transformation from MCI to AD. Moreover, we explored correlations between Apolipoprotein E4 and m6A methylations.
Collectively, these findings suggest that m6A methylations as potential biomarkers and therapeutic targets for cognitive dysfunction.
This work was supported by the National Natural Science Foundation of China (81871040) and the Shanghai Health System Talent Training Program (2018BR29).
N6 腺苷甲基化（m6A）是真核细胞中最丰富的内部 RNA 修饰。m6A 的失调与不同疾病中细胞增殖和细胞死亡的紊乱有关。然而，m6A 在神经退行性过程和认知功能障碍中的作用尚不清楚。
我们使用已发表的阿尔茨海默病（AD）、血管性痴呆和轻度认知障碍（MCI）数据集，系统地研究了 m6A 调节因子的分子改变及其与认知功能障碍的临床相关性。
m6A 调节因子的表达在不同组织中存在差异，并且与神经退行性途径密切相关。我们确定了共表达的 m6A 调节因子 SNRPG 和 SNRPD2 作为预测从 MCI 向 AD 转化的潜在生物标志物。此外，我们还探讨了载脂蛋白 E4 与 m6A 甲基化之间的相关性。
综上所述，这些发现表明 m6A 甲基化作为认知功能障碍的潜在生物标志物和治疗靶点。
本工作得到了国家自然科学基金（81871040）和上海市卫生系统人才培养计划（2018BR29）的支持。
