Ide

Case study 1: Ayse Yilmaz, 2023

Insulin-degrading enzyme (IDE) is a highly conserved metalloprotease that is mainly localized in the cytosol. Although IDE can degrade insulin and some other low molecular weight substrates efficiently, its ubiquitous expression suggests additional functions supported by experimental findings, such as a role in stress responses and cellular protein homeostasis. The translation of a long full-length IDE transcript has been reported to result in targeting to mitochondria, but the role of IDE in this compartment is unknown.

To obtain initial leads on the function of IDE in mitochondria, the researchers used a proximity biotinylation approach to identify proteins interacting with wild-type and protease-dead IDE targeted to the mitochondrial matrix. IDE interacts with multiple mitochondrial ribosomal proteins as well as with proteins involved in the synthesis and assembly of mitochondrial complex I and IV. The mitochondrial interactomes of wild type and mutant IDE are highly similar and do not reveal any likely proteolytic IDE substrates. IDE may adopt similar additional non-proteolytic functions in mitochondria as in the cytosol, acting as a chaperone and contributing to protein homeostasis and stress responses.

Fig1. The expression of TurboID fusion proteins in HEK293 cells.

Fig2. Confocal fluorescent imaging of HEK293 expressing TurboID fusion proteins.

Case study 2: Helen A Rowland, 2023

Alzheimer's disease (AD) is characterised by the aggregation and deposition of amyloid-β (Aβ) peptides in the human brain. In age-related late-onset AD, deficient degradation and clearance, rather than enhanced production, of Aβ contributes to disease pathology. In the present study, the researchers assessed the contribution of the two key Aβ-degrading zinc metalloproteases, insulin-degrading enzyme (IDE) and neprilysin (NEP), to Aβ degradation in human induced pluripotent stem cell (iPSC)-derived cortical neurons.

Using an Aβ fluorescence polarisation assay, inhibition of IDE but not of NEP, blocked the degradation of Aβ by human neurons. When the neurons were grown in a 3D extracellular matrix to visualise Aβ deposition, inhibition of IDE but not NEP, increased the number of Aβ deposits. Inhibition of the Aβ-forming β-secretase prevented the formation of the IDE-inhibited Aβ deposits. These data indicate that inhibition of IDE in live human neurons grown in a 3D matrix increased the deposition of Aβ derived from the proteolytic cleavage of the amyloid precursor protein.

Fig3. Incubation of the Aβ substrate (500 nM) with 25 ng recombinant IDE (rIDE) in the absence or presence of the general metalloprotease inhibitor 1,10-phenanthroline (1 mM), the IDE inhibitors 6bK (10 μM), ML345 (10 μM) and insulin (100 μM).

Fig4. Representative images of day 60 OX1-19 neurons cultured in a 3D Matrigel matrix for 21 days in the presence of the IDE inhibitor, ML345, with or without the BACE1 inhibitor βIV.

Fig1. Schematic illustration of possible signaling pathways involved in the improvement of AD-related cognitive impairment by IDE. (Yue Tian, 2023)

Fig2. Possible signaling pathways involved in IDE-mediated improvement in cognitive impairment in diabetes models. (Yue Tian, 2023)

Ide involved in several pathways and played different roles in them. We selected most pathways Ide participated on our site, such as Alzheimers disease, which may be useful for your reference. Also, other proteins which involved in the same pathway with Ide were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

Ide has several biochemical functions, for example, ATP binding, ATPase activity, beta-amyloid binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Ide itself. We selected most functions Ide had, and list some proteins which have the same functions with Ide. You can find most of the proteins on our site.

Ide has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Ide here. Most of them are supplied by our site. Hope this information will be useful for your research of Ide.

CCL3; SIRT4; CCL4; Cdk1; NES; IFIH1