Li Yuan Y, Alexandrov Peter N, Pogue Aileen I, Zhao Yuhai, Bhattacharjee Surjyadipta, Lukiw Walter J
Department of Ophthalmology, LSU Neuroscience Center, Louisiana State University Health Sciences Center, 2020 Gravier St., New Orleans, LA 70112, USA.
Neuroreport. 2012 Feb 15;23(3):168-73. doi: 10.1097/WNR.0b013e32834f4eb4.
Down's syndrome, a congenital disorder associated with cognitive impairment and early-onset Alzheimer's disease, is a progressive genetic pathology resulting from full or partial triplication of chromosome 21. Down's syndrome brain is typified by activated microglia, increases in inflammatory signaling, and an aberrant immune system. In these studies, a screening of micro-RNA (miRNA) from Down's syndrome brain and peripheral tissues indicated an upregulation of a chromosome 21-encoded miRNA-155 and a decrease in the abundance of the miRNA-155 mRNA target complement factor H (CFH), an important repressor of the innate immune response. Stressed primary human neuronal-glial cells indicated both miRNA-155 increase and CFH downregulation, an effect that was reversed using anti-miRNA-155. These findings suggest that immunopathological deficits associated with Down's syndrome can, in part, be explained by a generalized miRNA-155-mediated downregulation of CFH that may contribute to both brain and systemic immune pathology.
唐氏综合征是一种与认知障碍和早发性阿尔茨海默病相关的先天性疾病，是由21号染色体全部或部分三体化导致的一种进行性遗传病理状态。唐氏综合征患者的大脑以小胶质细胞活化、炎症信号增加和免疫系统异常为特征。在这些研究中，对唐氏综合征患者大脑和外周组织中的微小RNA（miRNA）进行筛查，结果显示21号染色体编码的miRNA-155上调，而miRNA-155 mRNA靶标补体因子H（CFH）（先天免疫反应的重要抑制因子）的丰度降低。对原代人神经胶质细胞施加应激后，miRNA-155增加且CFH下调，而使用抗miRNA-155可逆转这一效应。这些发现表明，唐氏综合征相关的免疫病理缺陷部分可由miRNA-155介导的CFH普遍下调来解释，这可能导致大脑和全身的免疫病理状态。
