Agostini Simone, Mancuso Roberta, Liuzzo Gaia, Bolognesi Elisabetta, Costa Andrea Saul, Bianchi Anna, Clerici Mario
IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Front Aging Neurosci. 2019 Mar 11;11:52. doi: 10.3389/fnagi.2019.00052. eCollection 2019.
MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by binding their 3' untranslated region (3'UTR) region; these molecules play a fundamental role in several pathologies, including Alzheimer's disease (AD). Synaptosomal-associated protein of 25 kDa (SNAP-25) is a vesicular protein of soluble -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) involved in neural plasticity and in the exocytosis of neurotransmitters, processes that are altered in AD. Recent results showed that a reduction of SNAP-25 is associated with dementia, and that the rs363050 SNAP-25 polymorphism correlates with cognitive decline and brain atrophy, as well as with the outcome of multistructured rehabilitation in AD patients. We verified the presence of possible correlations between the serum concentration of miRNAs that bind the SNAP-25 3'UTR region and AD. Six different microRNAs (miR-181a-5p, miR-361-3p, miR-23a-3p, miR-15b-3p, 130a-3p and miR-27b-3p) that bind the SNAP-25 3'UTR region were measured by qPCR in serum of AD patients ( = 22), mild cognitive impairment (MCI) subjects ( = 22) and age- and sex-matched controls ( = 22); analysis of results was done stratified for the rs363050 SNAP-25 genotype. Results showed that miR-27b-3p, miR-23a-3p and miR181a-5p serum concentration was significantly reduced in rs363050 SNAP-25 GG homozygous AD patients. Notably, concentration of these miRNAs was comparable in rs363050 AA homozygous AD patients, MCI and healthy controls (HCs). Data herein suggest that miRNAs that bind the SNAP-25 3'UTR region interact with SNAP-25 polymorphisms to influence the neural plasticity typical of AD brains, possibly as a consequence of modulatory activity on SNAP-25 mRNA and/or protein.
微小RNA（miRNA）是一类小的非编码RNA，通过结合其3'非翻译区（3'UTR）来控制基因表达；这些分子在包括阿尔茨海默病（AD）在内的多种病理过程中发挥着重要作用。25 kDa的突触体相关蛋白（SNAP - 25）是可溶性N - 乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）的一种囊泡蛋白，参与神经可塑性和神经递质的胞吐作用，而这些过程在AD中会发生改变。最近的研究结果表明，SNAP - 25的减少与痴呆症相关，并且rs363050 SNAP - 25多态性与认知能力下降、脑萎缩以及AD患者多结构康复的结果相关。我们验证了结合SNAP - 25 3'UTR区域的miRNA血清浓度与AD之间可能存在的相关性。通过qPCR检测了AD患者（n = 22）、轻度认知障碍（MCI）受试者（n = 22）以及年龄和性别匹配的对照组（n = 22）血清中六种结合SNAP - 25 3'UTR区域的不同微小RNA（miR - 181a - 5p、miR - 361 - 3p、miR - 23a - 3p、miR - 15b - 3p、130a - 3p和miR - 27b - 3p）；根据rs363050 SNAP - 25基因型对结果进行分层分析。结果显示，rs363050 SNAP - 25 GG纯合子AD患者血清中miR - 27b - 3p、miR - 23a - 3p和miR181a - 5p的浓度显著降低。值得注意的是，这些miRNA的浓度在rs363050 AA纯合子AD患者、MCI患者和健康对照（HC）中相当。本文数据表明，结合SNAP - 25 3'UTR区域的miRNA与SNAP - 25多态性相互作用，以影响AD大脑典型的神经可塑性，这可能是对SNAP - 25 mRNA和/或蛋白质调节活性的结果。
