Evidence map›Paper›PMID 37759469›Full record

ArticleCells2023

Obatoclax Rescues FUS-ALS Phenotypes in iPSC-Derived Neurons by Inducing Autophagy.

Cristina Marisol Castillo Bautista, Kristin Eismann, Marc Gentzel, Silvia Pelucchi, Jerome Mertens, Hannah E Walters, Maximina H Yun, Jared Sterneckert

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.6field-weighted citation impact, top 29% of its field
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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. 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

8 authors at 5 institutions in 4 countries.

Cristina Marisol Castillo BautistaCenter for Regenerative Therapies TU Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany.
Kristin EismannCore Facility Mass Spectrometry & Proteomics, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, 01307 Dresden, Germany.
Marc GentzelCore Facility Mass Spectrometry & Proteomics, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, 01307 Dresden, Germany.ORCID 0000-0002-4482-6010
Silvia PelucchiDepartment of Neurosciences, University of California San Diego, La Jolla, CA 92161, USA.
Jerome MertensDepartment of Neurosciences, University of California San Diego, La Jolla, CA 92161, USA.ORCID 0000-0002-4291-4121
Hannah E WaltersCenter for Regenerative Therapies TU Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany.
Maximina H YunCenter for Regenerative Therapies TU Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany.ORCID 0000-0001-9019-2453
Jared SterneckertCenter for Regenerative Therapies TU Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany.ORCID 0000-0002-7688-3124
Technische Universität Dresden · DEMax Planck Institute of Molecular Cell Biology and Genetics · DESalk Institute for Biological Studies · USUniversity Hospital Carl Gustav Carus · DEUniversity of Milan · IT

Funding

UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DOUGLAS R GALASKO · 2019 to 2026
$34.9M
ConProject-002RF1AG056306 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI GAGE, FRED H · 2022 to 2025
$2.8M
Assessing cellular aging in old and rejuvenated neurons from Alzheimer patientsR01AG056306 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI GAGE, FRED H · 2017 to 2021
$2.4M
European Research Council ERC-STG-2019-852086NIA NIH HHS AG056306NIA NIH HHS P30 AG062429NIA NIH HHS R01 AG056306NIA NIH HHS RF1 AG056306
6 · The paper itself

Abstract

Aging is associated with the disruption of protein homeostasis and causally contributes to multiple diseases, including amyotrophic lateral sclerosis (ALS). One strategy for restoring protein homeostasis and protecting neurons against age-dependent diseases such as ALS is to de-repress autophagy. BECN1 is a master regulator of autophagy; however, is repressed by BCL2 via a BH3 domain-mediated interaction. We used an induced pluripotent stem cell model of ALS caused by mutant FUS to identify a small molecule BH3 mimetic that disrupts the BECN1-BCL2 interaction. We identified obatoclax as a brain-penetrant drug candidate that rescued neurons at nanomolar concentrations by reducing cytoplasmic FUS levels, restoring protein homeostasis, and reducing degeneration. Proteomics data suggest that obatoclax protects neurons via multiple mechanisms. Thus, obatoclax is a candidate for repurposing as a possible ALS therapeutic and, potentially, for other age-associated disorders linked to defects in protein homeostasis.

Indexed as

Amyotrophic Lateral SclerosisInduced Pluripotent Stem CellsAutophagyHumansIndolesMotor NeuronsMutationPhenotypeProto-Oncogene Proteins c-bcl-2PyrrolesRNA-Binding Protein FUSFUS protein, humanIndolesobatoclaxProto-Oncogene Proteins c-bcl-2PyrrolesRNA-Binding Protein FUSamyotrophic lateral sclerosisautophagyFUSphenotypic screening

Identifiers

PMID37759469
PMCPMC10527391
OpenAlexW4386602057

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.