Evidence mapPaperPMID 34572094Full record

ArticleCells2021

Insulin-Degrading Enzyme: Paradoxes and Possibilities.

Malcolm A Leissring

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.8field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
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  15. Disentangling Mitochondria in Alzheimer's Disease.International journal of molecular sciences · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

1 author at 1 institution in 1 country.

Malcolm A LeissringInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine (UCI MIND), Irvine, CA 92697, USA.ORCID 0000-0001-7185-4255
University of California, Irvine · US

Funding

Temporal and spatial aspects of amyloidogenesis in sporadic Alzheimer diseaseR01AG066928 · UNIVERSITY OF CALIFORNIA-IRVINE · 2025 to 2025
$542k
NIA NIH HHS R01 AG066928NIGMS NIH HHS R01 GM115617NIGMS NIH HHS R21 GM140283NIH HHS AG066928NIH HHS GM115617NIH HHS GM140283
6 · The paper itself

Abstract

More than seven decades have passed since the discovery of a proteolytic activity within crude tissue extracts that would become known as insulin-degrading enzyme (IDE). Certainly much has been learned about this atypical zinc-metallopeptidase; at the same time, however, many quite fundamental gaps in our understanding remain. Herein, I outline what I consider to be among the most critical unresolved questions within the field, many presenting as intriguing paradoxes. For instance, where does IDE, a predominantly cytosolic protein with no signal peptide or clearly identified secretion mechanism, interact with insulin and other extracellular substrates? Where precisely is IDE localized within the cell, and what are its functional roles in these compartments? How does IDE, a bowl-shaped protein that completely encapsulates its substrates, manage to avoid getting "clogged" and thus rendered inactive virtually immediately? Although these paradoxes are by definition unresolved, I offer herein my personal insights and informed speculations based on two decades working on the biology and pharmacology of IDE and suggest specific experimental strategies for addressing these conundrums. I also offer what I believe to be especially fruitful avenues for investigation made possible by the development of new technologies and IDE-specific reagents. It is my hope that these thoughts will contribute to continued progress elucidating the physiology and pathophysiology of this important peptidase.

Indexed as

AnimalsHumansInsulinInsulysinInsulinInsulysindiabetes mellitusinsulininsulin-degrading enzymeprotease inhibitorsproteolysis

Identifiers

PMID34572094
PMCPMC8472535
OpenAlexW3201241167

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.