Evidence map›Paper›PMID 36945394›Full record

ArticlebioRxiv : the preprint server for biology2023

Aberrant phase separation is a common killing strategy of positively charged peptides in biology and human disease.

Steven Boeynaems, X Rosa Ma, Vivian Yeong, Garrett M Ginell, Jian-Hua Chen, Jacob A Blum, Lisa Nakayama, Anushka Sanyal, Adam Briner, Delphi Van Haver and 13 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 14 citations in OpenAlex.

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

23 authors at 10 institutions in 4 countries.

Steven BoeynaemsDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
X Rosa MaDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Vivian YeongDepartment of Chemical Engineering, Columbia University, New York, NY, 10027, USA.
Garrett M GinellDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jian-Hua ChenMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Jacob A BlumDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lisa NakayamaDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Anushka SanyalDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Adam BrinerClem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland, Brisbane, QLD 4072, Australia.
Delphi Van HaverVIB-UGent Center for Medical Biotechnology, 9000 Gent, Belgium.
Jarne PauwelsVIB-UGent Center for Medical Biotechnology, 9000 Gent, Belgium.
Axel EkmanMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
H Broder SchmidtDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kousik SundararajanDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lucas PortaDepartment of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), Sao Paulo, Brazil.
Keren LaskerDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Carolyn LarabellMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Mirian A F HayashiDepartment of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), Sao Paulo, Brazil.
Anshul KundajeDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Francis ImpensVIB-UGent Center for Medical Biotechnology, 9000 Gent, Belgium.
Allie ObermeyerDepartment of Chemical Engineering, Columbia University, New York, NY, 10027, USA.
Alex S HolehouseDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Aaron D GitlerDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Stanford University · USGhent University · BELawrence Berkeley National Laboratory · USColumbia University · USUniversidade Federal de São Paulo · BRWashington University in St. Louis · USBaylor College of Medicine · USChan Zuckerberg Initiative (United States) · USScripps Research Institute · USThe University of Queensland · AU

Funding

Training Program in Basic NeuroscienceT32MH020016 · NIMH · STANFORD UNIVERSITY · PI Justin L Gardner, Merritt C Maduke · 1997 to 2026
$16.2M
Innovating Yeast and Human Genetics Approaches to Define Mechanisms of Neurodegenerative DiseaseR35NS097263 · NINDS · STANFORD UNIVERSITY · PI GITLER, AARON D. · 2017 to 2024
$8.6M
TrainingP41GM103445 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LARABELL, CAROLYN A · 2012 to 2019
$8.2M
VECTOR COREP30NS069375 · NINDS · STANFORD UNIVERSITY · PI STEINBERG, GARY K · 2011 to 2019
$6.3M
User Training and OutreachP30GM138441 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LARABELL, CAROLYN A · 2020 to 2023
$3.7M
NIGMS NIH HHS P30 GM138441NIGMS NIH HHS P41 GM103445NIMH NIH HHS T32 MH020016NINDS NIH HHS P30 NS069375NINDS NIH HHS R35 NS097263
6 · The paper itself

Abstract

Positively charged repeat peptides are emerging as key players in neurodegenerative diseases. These peptides can perturb diverse cellular pathways but a unifying framework for how such promiscuous toxicity arises has remained elusive. We used mass-spectrometry-based proteomics to define the protein targets of these neurotoxic peptides and found that they all share similar sequence features that drive their aberrant condensation with these positively charged peptides. We trained a machine learning algorithm to detect such sequence features and unexpectedly discovered that this mode of toxicity is not limited to human repeat expansion disorders but has evolved countless times across the tree of life in the form of cationic antimicrobial and venom peptides. We demonstrate that an excess in positive charge is necessary and sufficient for this killer activity, which we name 'polycation poisoning'. These findings reveal an ancient and conserved mechanism and inform ways to leverage its design rules for new generations of bioactive peptides.

Indexed as

amyotrophic lateral sclerosisantimicrobial peptidecathelicidincrotaminefrontotemporal dementiaLL-37membraneless organellesPhase separationprotein aggregationRAN translation

Identifiers

PMID36945394
PMCPMC10028949
OpenAlexW4323657478

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.