PXD039670

PXD039670 is an original dataset announced via ProteomeXchange.

Title	The small molecule lipoamide modulates stress granule condensation with beneficial outcomes for familial amyotrophic lateral sclerosis models
Description	Neurodegenerative diseases like amyotrophic lateral sclerosis are often associated with mutations in proteins which can form stress granules by liquid-liquid phase separation (LLPS). Formation of these condensate phases requires a complex molecular grammar for protein-protein interactions which, when aberrant, can lead to altered condensation and disease phenotypes. We asked whether condensation of ALS-associated proteins could be a drug target. Screening identified lipoamide, a small molecule which specifically reduces cytoplasmic condensation (stress granules) of FUS and other ALS-associated proteins. In vitro, lipoamide partitions into and alters the physical properties of condensates made by FUS, similarly in cells lipoamide partitions into stress granules. Thermal proteome profiling showed lipoamide stabilises proteins with R/Y-rich intrinsically disordered domains in cells, including SRSF1 and SFPQ, two stress granule proteins which are necessary for lipoamide activity. In animals, lipoamide reduces aging-associated aggregation of a stress granule protein and improves neuronal morphology and recovers motor defects caused by ALS-associated FUS and TDP43 mutations. Lipoamide is a well-tolerated specific small molecule modulator of stress granule condensation with drug-like potential.
HostingRepository	PRIDE
AnnounceDate	2025-05-09
AnnouncementXML	Submission_2025-05-09_05:41:18.097.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Stengel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-25 09:11:13	ID requested
⏵ 1	2025-05-09 05:41:18	announced

Dataset with its publication pending

submitter keyword: stress granule, small molecules, amyotrophic lateral sclerosis,Molecular condensates, liquid-liquid phase separation

Florian Stengel
contact affiliation	Department of Biology, University of Konstanz, Universitaetsstrasse 10, 78457 Konstanz, Germany
contact email	florian.stengel@uni-konstanz.de
lab head
Florian Stengel
contact affiliation	Universität Konstanz
contact email	florian.stengel@uni-konstanz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039670
     1. Label: PRIDE project
     2. Name: The small molecule lipoamide modulates stress granule condensation with beneficial outcomes for familial amyotrophic lateral sclerosis models