New Insights on the Regulation of the Insulin-Degrading Enzyme: Role of microRNAs and RBPs

The evident implication of the insulin-degrading enzyme (IDE) in Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM), among its capacity to degrade insulin and amyloid-β peptide (Aβ), suggests that IDE could be an essential link in the relation between hyperinsulinemia, insulin resistance and AD. However, little is known about the cellular and molecular regulation of IDE expression, and even less has been explored regarding the post-transcriptional regulation of IDE, although it represents a great molecular target of interest for therapeutic treatments. We recently described that miR-7, a novel candidate for linking AD and T2DM at the molecular level, regulates IDE and other key genes in both pathologies, including some key genes involved in the insulin signaling pathway. Here, we explored whether other miRNAs as well as other post-transcriptional regulators, such as RNA binding proteins (RBP), could potentially participate in the regulation of IDE expression in vitro. Our data showed that in addition to miR-7, miR-125, miR-490 and miR-199 regulate IDE expression at the post-transcriptional level. Moreover, we also found that IDE contains multiple potential binding sites for several RBPs, and a narrow-down prediction analysis led us to speculate on a novel regulation of IDE by RALY and HuD. Taken together, these results demonstrate the novel players controlling IDE expression that could represent potential therapeutical targets to treat several metabolic diseases with a high impact on human health, including AD and T2DM.

• Publication year

  2022

• Venue

  Cells

• Publication date

  2022-08-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/cells11162538PMID 36010613PMCID 9406717
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• OUP accepted manuscript

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