Evidence map›Paper›PMID 39362844›Full record

ArticleNature communications2024

Cathepsin B promotes Aβ proteotoxicity by modulating aging regulating mechanisms.

Atif Ahmed Siddiqui, Emmanuelle Merquiol, Reut Bruck-Haimson, Joud Hirbawi, Hana Boocholez, Irit Cohen, Yonghong Yan, Meng Qiu Dong, Galia Blum, Ehud Cohen

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026
    Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
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

10 authors.

Atif Ahmed SiddiquiDepartment of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada (IMRIC) The Hebrew University, Jerusalem, 9112001, Israel.
Emmanuelle MerquiolInstitute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem, 9112001, Israel.ORCID 0000-0001-5754-498X
Reut Bruck-HaimsonDepartment of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada (IMRIC) The Hebrew University, Jerusalem, 9112001, Israel.
Joud HirbawiDepartment of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada (IMRIC) The Hebrew University, Jerusalem, 9112001, Israel.
Hana BoocholezDepartment of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada (IMRIC) The Hebrew University, Jerusalem, 9112001, Israel.
Irit CohenDepartment of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada (IMRIC) The Hebrew University, Jerusalem, 9112001, Israel.
Yonghong YanNational Institute of Biological Sciences (NIBS), 102206, Beijing, China.
Meng Qiu DongNational Institute of Biological Sciences (NIBS), 102206, Beijing, China.ORCID 0000-0002-6094-1182
Galia BlumInstitute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem, 9112001, Israel. galiabl@ekmd.huji.ac.il.ORCID 0000-0002-9374-2489
Ehud CohenDepartment of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada (IMRIC) The Hebrew University, Jerusalem, 9112001, Israel. ehudc@ekmd.huji.ac.il.ORCID 0000-0001-5552-7086

Funding

Israel Science Foundation (ISF) 3261/20Israel Science Foundation (ISF) 543/21Israel Science Foundation (ISF) GB#1638/19
6 · The paper itself

Abstract

While the activities of certain proteases promote proteostasis and prevent neurodegeneration-associated phenotypes, the protease cathepsin B (CTSB) enhances proteotoxicity in Alzheimer's disease (AD) model mice, and its levels are elevated in brains of AD patients. How CTSB exacerbates the toxicity of the AD-causing Amyloid β (Aβ) peptide is controversial. Using an activity-based probe, aging-altering interventions and the nematode C. elegans, we discovered that the CTSB CPR-6 promotes Aβ proteotoxicity but mitigates the toxicity of polyQ stretches. While the knockdown of cpr-6 does not affect lifespan, it alleviates Aβ toxicity by reducing the expression of swsn-3 and elevating the level of the protein SMK-1, both involved in the regulation of aging. These observations unveil a mechanism by which CTSB aggravates Aβ-mediated toxicity, indicate that it plays opposing roles in the face of distinct proteotoxic insults and highlight the importance of tailoring specific remedies for distinct neurodegenerative disorders.

Indexed as

AgingAlzheimer DiseaseAmyloid beta-PeptidesCaenorhabditis elegansCaenorhabditis elegans ProteinsCathepsin BAnimalsDisease Models, AnimalAmyloid beta-PeptidesCaenorhabditis elegans ProteinsCathepsin B

Identifiers

PMID39362844
PMCPMC11450018

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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 OpenQuestion graph.