Evidence map›Paper›PMID 41497660›Full record

ArticlebioRxiv : the preprint server for biology2025

Cathepsin C-Catalyzed Ligation Generates Intralysosomal Amyloid Fibrils from Dipeptide Esters.

Ruben D Elias, Robert T O'Neill, Idil I Demiralp, Seth Allen, Daniel Serwas, Hannah Siems, Elizabeth A Montabana, Carl Ash, Daniella A Yacoubian, Oren L Lederberg and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Ruben D EliasDepartment of Chemistry, The Scripps Research Institute; La Jolla, CA, USA.
Robert T O'NeillDepartment of Chemistry, The Scripps Research Institute; La Jolla, CA, USA.
Idil I DemiralpDepartment of Chemistry, The Scripps Research Institute; La Jolla, CA, USA.
Seth AllenDepartment of Chemistry, The Scripps Research Institute; La Jolla, CA, USA.
Daniel SerwasBiohub, San Francisco; Redwood City, CA, USA.
Hannah SiemsBiohub, San Francisco; Redwood City, CA, USA.
Elizabeth A MontabanaBiohub, San Francisco; Redwood City, CA, USA.
Carl AshDepartment of Chemistry, The Scripps Research Institute; La Jolla, CA, USA.
Daniella A YacoubianDepartment of Chemistry, The Scripps Research Institute; La Jolla, CA, USA.
Oren L LederbergDepartment of Chemistry, The Scripps Research Institute; La Jolla, CA, USA.
Benjamin F CravattDepartment of Chemistry, The Scripps Research Institute; La Jolla, CA, USA.
David A AgardBiohub, San Francisco; Redwood City, CA, USA.
Jeffery W KellyDepartment of Chemistry, The Scripps Research Institute; La Jolla, CA, USA.

Funding

Pharmacologic Lysosomal Flux Activators to Ameliorate Alzheimer's Disease and Related DementiasRF1AG073418 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI KELLY, JEFFERY W · 2021 to 2021
$2.6M
CTSA Postdoctoral T32 at The Scripps Research InstituteT32TR004396 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI Katja A Lamia, Luc Teyton · 2024 to 2026
$770k
NCATS NIH HHS T32 TR004396NIA NIH HHS RF1 AG073418
6 · The paper itself

Abstract

Amyloid fibril-associated endolysosomal dysfunction is implicated in multiple neurodegenerative diseases. We report the rapid generation of intralysosomal amyloid fibrils by simply treating cells with certain dipeptide methyl esters. Cathepsin C mediates the ligation of dipeptides into oligopeptides that, sequence-dependently, self-assemble into amyloid fibrils. Progressive fibril growth, not fibril deposition, mediates lysosomal membrane permeabilization. Cryo-electron tomography studies reveal intralysosomal fibrils and broken lysosomal membranes upon dipeptide treatment. Certain oligopeptide fibril structures are competent to cross-seed the aggregation of neurodegeneration-associated Tau(P301S) at lysosomal sites. Similarly, the degree of lysosomal membrane permeabilization and ESCRT-repair response can be tuned with dipeptide sequence variation. The presented Cathepsin C-dependent amyloid fibril formation approach lends itself toward the development of novel tools to further probe lysosomal biology and pathobiology.

Identifiers

PMID41497660
PMCPMC12767319

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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.