Determination of miR-373 and miR-204 levels in neuronal exosomes in Alzheimer?s disease

Authors: ELİFCAN TAŞDELEN, ERGUVAN TUĞBA ÖZEL KIZIL, SABİHA TEZCAN AYDEMİR, ÖMER ERAY YALAP, AYŞE PETEK BİNGÖL, NÜKET KUTLAY

Abstract: Background/aim: NLRP3 inflammasome activation has been known to be involved in the etiology and progression of Alzheimer?s disease (AD). Furthermore, AD and diabetes mellitus have common pathomechanisms. It has been shown that P2X7R whose expression is increased in brain tissues with AD and plays a role in the activation of NLRP3 inflammasome is suppressed by miR-373 in patients with osteoarthritis. Therefore, the question of whether the suppressive effect of miR-373 on NLRP3 may have a role in the pathophysiology of AD comes to mind. On the other hand, it is known that the miR-204 level increases in response to TXNIP, another NLRP3 inflammasome inducer with high expression in AD. In primary human islets, miR-204 reduces the expression of GLP-1R. It has been discovered that in vivo deletion of miR-204 is protective against diabetes by increasing GLP-1R and insulin secretion. Considering the relationship between miR-204 and TXNIP and the relationship of miR-204 with diabetes suggests investigating the effect of miR-204 on the inflammatory pathway in AD. Based on the common pathophysiological mechanisms between AD and diabetes and the reported changes related to NLRP3 inflammasome, we analyzed miR-373 and miR-204 in neuron-derived serum exosomes in this study. Neuronderived exosomes in neurodegenerative diseases are considered to be better candidates for developing potential biomarkers. Materials and methods: The expression levels of miR-204 and miR-373 were investigated in neuron-derived serum exosomes obtained from 15 patients with mild AD, 18 with moderate AD, and 21 cognitively healthy individuals. Results and discussion: The miR-204 and miR-373 expressions were significantly decreased in both patient groups compared to the control group. Therefore, we suggest that miR-204 and miR-373 are potential biomarkers for AD. However, due to the preliminary nature of this study, further large-scale studies are needed to support our findings.

Keywords: MiR-204, miR-373, Alzheimer?s disease, neuron derived exosomes, NLRP3 inflammasome, TXNIP, P2X7R, GLP-1R

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