Evidence mapPaperPMID 39610243Full record

ArticleCell2025

Proteolethargy is a pathogenic mechanism in chronic disease.

Alessandra Dall'Agnese, Ming M Zheng, Shannon Moreno, Jesse M Platt, An T Hoang, Deepti Kannan, Giuseppe Dall'Agnese, Kalon J Overholt, Ido Sagi, Nancy M Hannett and 5 more

Abstract read
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
field-weighted citation impact
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

12 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Causality of Aging Hallmarks.Aging and disease · 2025
    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

15 authors.

Alessandra Dall'AgneseWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Ming M ZhengWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Shannon MorenoWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jesse M PlattWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
An T HoangWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Deepti KannanDepartment of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Giuseppe Dall'AgneseWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Kalon J OverholtWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ido SagiWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Nancy M HannettWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Hailey ErbWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Olivia CorradinWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Arup K ChakrabortyDepartment of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
Tong Ihn LeeWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. Electronic address: tlee@wi.mit.edu.
Richard A YoungWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: young@wi.mit.edu.

Funding

Project 4: Targeting genomic instability and evolution in myelomaP01CA155258 · NCI · DANA-FARBER CANCER INST · 2023 to 2025
$7.4M
Transcriptional regulation in mammalian cellsR35GM144283 · NIGMS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · 2022 to 2025
$1.6M
NCATS NIH HHS KL2 TR002542NCI NIH HHS P01 CA155258NIGMS NIH HHS R35 GM144283
6 · The paper itself

Abstract

The pathogenic mechanisms of many diseases are well understood at the molecular level, but there are prevalent syndromes associated with pathogenic signaling, such as diabetes and chronic inflammation, where our understanding is more limited. Here, we report that pathogenic signaling suppresses the mobility of a spectrum of proteins that play essential roles in cellular functions known to be dysregulated in these chronic diseases. The reduced protein mobility, which we call proteolethargy, was linked to cysteine residues in the affected proteins and signaling-related increases in excess reactive oxygen species. Diverse pathogenic stimuli, including hyperglycemia, dyslipidemia, and inflammation, produce similar reduced protein mobility phenotypes. We propose that proteolethargy is an overlooked cellular mechanism that may account for various pathogenic features of diverse chronic diseases.

Indexed as

ProteinsAnimalsChronic DiseaseCysteineHumansInflammationMiceReactive Oxygen SpeciesSignal TransductionCysteineProteinsReactive Oxygen Specieschronic diseasecysteineprotein mobilityproteolethargyreactive oxygen speciessignaling

Identifiers

PMID39610243
PMCPMC11724756

What Socratic holds

Textmetadata
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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.