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

Autor(es)

Manzine, Patricia R. ^[1] ; Pelucchi, Silvia ^{[2, 3]} ; Horst, Maria A. ^[4] ; Vale, Francisco A. C. ^[5] ; Pavarini, Sofia C. I. ^[1] ; Audano, Matteo ^[2] ; Mitro, Nico ^[2] ; Di Luca, Monica ^[2] ; Marcello, Elena ^[2] ; Cominetti, Marcia R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Dept Gerontol, Sao Carlos, SP - Brazil

^[2] Univ Milan, Dept Pharmacol & Biomol Sci, Milan - Italy

^[3] Univ Florence, Sect Pharmacol & Toxicol, Dept Neurosci Psychol Drug Res & Child Hlth, Florence - Italy

^[4] Univ Fed Goias, Fac Nutr, Goiania, Go - Brazil

^[5] Univ Fed Sao Carlos, Dept Med, Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF ALZHEIMER'S DISEASE; v. 61, n. 1, p. 113-123, 2018.
• Citações Web of Science: 9

Resumo

ADAM10 is the alpha-secretase that cleaves amyloid-beta 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 expressedmiRNAs were validated in a sample of 21ADsubjects 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. (AU)

• Processo FAPESP: 13/06879-4 - Biomarcadores sanguíneos para a Doença de Alzheimer: avaliação da expressão gênica da ADAM10 e de microRNAs
• Beneficiário: Márcia Regina Cominetti
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/08654-7 - Biomarcadores sanguíneos para a Doença de Alzheimer: avaliação da expressão gênica da ADAM10 e de micro-RNAs
• Beneficiário: Patricia Regina Manzine Moralles
• Modalidade de apoio: Bolsas no Brasil - Doutorado