Yang Guoshuai, Song Yanmin, Zhou Xiaoyan, Deng Yidong, Liu Tao, Weng Guohu, Yu Dan, Pan Suyue
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Mol Med Rep. 2015 Aug;12(2):3081-8. doi: 10.3892/mmr.2015.3728. Epub 2015 May 5.
Alzheimer's disease (AD), characterized by β-amyloid deposition and neurodegeneration, is the most common cause of dementia worldwide. Emerging evidence suggests that ectopic expression of micro (mi)RNAs is involved in the pathogenesis of AD. There is increasing evidence that miRNAs expressed in the brain are involved in neuronal development, survival and apoptosis. The expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is regulated by dysregulated miRNAs in the brain. The present study determined the expression levels of the miRNA-29 (miR-29) family in peripheral blood samples of patients with AD and demonstrated a marked decrease in the expression of miR-29c compared with age-matched controls. In addition, a significant increase in the expression of BACE1 was observed in the peripheral blood of patients with AD. Correlation analysis revealed that the expression of miR-29c was negatively correlated with the protein expression of BACE1 in the peripheral blood samples from patients with AD. The present study also investigated the role of miR-29 on hippocampal neurons in vitro and in vivo. The results demonstrated that the upregulation of miR-29c promoted learning and memory behaviors in SAMP8 mice, at least partially, by increasing the activity of protein kinase A/cAMP response element-binding protein, involved in neuroprotection. This evidence suggested that miR-29c may be a promising potential therapeutic target against AD.
阿尔茨海默病（AD）以β-淀粉样蛋白沉积和神经退行性病变为特征，是全球范围内痴呆最常见的病因。新出现的证据表明，微小（mi）RNA的异位表达参与了AD的发病机制。越来越多的证据表明，大脑中表达的miRNA参与神经元的发育、存活和凋亡。β-位点淀粉样前体蛋白裂解酶1（BACE1）的表达受大脑中失调的miRNA调控。本研究测定了AD患者外周血样本中miRNA-29（miR-29）家族的表达水平，结果显示与年龄匹配的对照组相比，miR-29c的表达显著降低。此外，在AD患者的外周血中观察到BACE1的表达显著增加。相关性分析显示，在AD患者外周血样本中，miR-29c的表达与BACE1的蛋白表达呈负相关。本研究还在体外和体内研究了miR-29对海马神经元的作用。结果表明，miR-29c的上调至少部分通过增加参与神经保护的蛋白激酶A/环磷酸腺苷反应元件结合蛋白的活性，促进了SAMP8小鼠的学习和记忆行为。这一证据表明，miR-29c可能是一种有前景的抗AD潜在治疗靶点。
