ADAM10 is the α-secretase that cleaves amyloid-β protein precursor in the non-amyloidogenic pathway in Alzheimer's disease (AD) and is known to be regulated by different microRNAs (miRNAs), which are post-transcriptional regulators related to several biological and pathological processes, including AD. Here we proposed to explore and validate miRNAs that have direct or indirect relations to the AD pathophysiology and ADAM10 gene. Approximately 700 miRNAs were analyzed and 21 differentially expressed miRNAs were validated in a sample of 21 AD subjects and 17 cognitively healthy matched controls. SH-SY5Y cells were transfected with miR-144-5p, miR-221, and miR-374 mimics and inhibitors, and ADAM10 protein levels were evaluated. miR-144-5p, miR-221, and miR-374 were downregulated in AD. The overexpression of miR-221 in SH-SY5Y cells resulted in ADAM10 reduction and its inhibition in ADAM10 increased. These findings show that miR-221 can be a new potential therapeutic target for increasing ADAM10 levels in AD. In addition, these results can contribute to the better understanding of ADAM10 post-transcriptional regulation.

MicroRNA 221 Targets ADAM10 mRNA and is Downregulated in Alzheimer's Disease / P.R. Manzine, S. Pelucchi, M.A. Horst, F.A. Vale, S.C.I. Pavarini, M. Audano, N. Mitro, M. Di Luca, E. Marcello, M.R. Cominetti. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 61:1(2018), pp. 113-123. [10.3233/JAD-170592]

MicroRNA 221 Targets ADAM10 mRNA and is Downregulated in Alzheimer's Disease

S. Pelucchi;M. Audano;N. Mitro;M. Di Luca;E. Marcello;
2018

Abstract

ADAM10 is the α-secretase that cleaves amyloid-β protein precursor in the non-amyloidogenic pathway in Alzheimer's disease (AD) and is known to be regulated by different microRNAs (miRNAs), which are post-transcriptional regulators related to several biological and pathological processes, including AD. Here we proposed to explore and validate miRNAs that have direct or indirect relations to the AD pathophysiology and ADAM10 gene. Approximately 700 miRNAs were analyzed and 21 differentially expressed miRNAs were validated in a sample of 21 AD subjects and 17 cognitively healthy matched controls. SH-SY5Y cells were transfected with miR-144-5p, miR-221, and miR-374 mimics and inhibitors, and ADAM10 protein levels were evaluated. miR-144-5p, miR-221, and miR-374 were downregulated in AD. The overexpression of miR-221 in SH-SY5Y cells resulted in ADAM10 reduction and its inhibition in ADAM10 increased. These findings show that miR-221 can be a new potential therapeutic target for increasing ADAM10 levels in AD. In addition, these results can contribute to the better understanding of ADAM10 post-transcriptional regulation.
ADAM10 protein; aging; Alzheimer's disease; biomarkers; microRNAs; clinical psychology; geriatrics and gerontology; psychiatry and mental health
Settore BIO/10 - Biochimica
Settore BIO/14 - Farmacologia
2018
2017
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/548143
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