Evidence map›Paper›PMID 39080379›Full record

ArticleScientific reports2024

TRPML1 activation ameliorates lysosomal phenotypes in CLN3 deficient retinal pigment epithelial cells.

D Wünkhaus, R Tang, K Nyame, N N Laqtom, M Schweizer, A Scotto Rosato, E K Krogsæter, C Wollnik, M Abu-Remaileh, C Grimm and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Reversible synaptic deficits in early-stage batten disease.Journal of translational medicine · 2026
    Article
  3. Article
  4. Article
  5. Lysosomes' fallback strategies: more than just survival or death.Frontiers in cell and developmental biology · 2025
    Review
  6. Article
  7. 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

14 authors.

D WünkhausEvotec SE, Hamburg, Germany.
R TangFaculty of Medicine, Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität, Munich, Germany.
K NyameDepartment of Chemical Engineering and of Genetics and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
N N LaqtomDepartment of Chemical Engineering and of Genetics and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
M SchweizerCore Facility Morphology and Electronmicroscopy, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
A Scotto RosatoFaculty of Medicine, Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität, Munich, Germany.
E K KrogsæterFaculty of Medicine, Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität, Munich, Germany.
C WollnikEvotec SE, Hamburg, Germany.
M Abu-RemailehDepartment of Chemical Engineering and of Genetics and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
C GrimmFaculty of Medicine, Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität, Munich, Germany.
G HermeyInstitute for Molecular and Cellular Cognition, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
R KuhnEvotec SE, Hamburg, Germany.
D Gruber-SchoffneggerEvotec SE, Hamburg, Germany.
S MarkmannEvotec SE, Hamburg, Germany. sandra.markmann@evotec.com.

Funding

Deutsche Forschungsgemeinschaft HE 3220/4-1
6 · The paper itself

Abstract

Mutations in the lysosomal membrane protein CLN3 cause Juvenile Neuronal Ceroid Lipofuscinosis (JNCL). Activation of the lysosomal ion channel TRPML1 has previously been shown to be beneficial in several neurodegenerative disease models. Here, we tested whether TRPML1 activation rescues disease-associated phenotypes in CLN3-deficient retinal pigment epithelial (ARPE-19 CLN3-KO) cells. ARPE-19 CLN3-KO cells accumulate LAMP1 positive organelles and show lysosomal storage of mitochondrial ATPase subunit C (SubC), globotriaosylceramide (Gb3), and glycerophosphodiesters (GPDs), whereas lysosomal bis(monoacylglycero)phosphate (BMP/LBPA) lipid levels were significantly decreased. Activation of TRPML1 reduced lysosomal storage of Gb3 and SubC but failed to restore BMP levels in CLN3-KO cells. TRPML1-mediated decrease of storage was TFEB-independent, and we identified TRPML1-mediated enhanced lysosomal exocytosis as a likely mechanism for clearing storage including GPDs. Therefore, ARPE-19 CLN3-KO cells represent a human cell model for CLN3 disease showing many of the described core lysosomal deficits, some of which can be improved using TRPML1 agonists.

Indexed as

LysosomesMembrane GlycoproteinsMolecular ChaperonesNeuronal Ceroid-LipofuscinosesRetinal Pigment EpitheliumTransient Receptor Potential ChannelsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell LineExocytosisHumansLysophospholipidsMonoglyceridesPhenotypeBasic Helix-Loop-Helix Leucine Zipper Transcription Factorsbis(monoacylglyceryl)phosphateCLN3 protein, humanLysophospholipidsMCOLN1 protein, humanMembrane GlycoproteinsMolecular ChaperonesMonoglyceridesTFEB protein, humanTransient Receptor Potential Channels

Identifiers

PMID39080379
PMCPMC11289453

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.