Evidence map›Paper›PMID 40049159›Full record

ArticleNeuron2025

KCTD20 suppression mitigates excitotoxicity in tauopathy patient organoids.

Joshua E Berlind, Jesse D Lai, Cecilia Lie, Jokabeth Vicente, Kelsey Lam, Sheron Guo, Jonathan Chang, Violeta Yu, Justin K Ichida

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

9 authors.

Joshua E BerlindDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA, USA.
Jesse D LaiDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA, USA; Department of Neuroscience, Amgen Inc., Cambridge, MA, USA; Neurological & Rare Diseases, Dewpoint Therapeutics, Boston, MA, USA. Electronic address: jesselai91@gmail.com.
Cecilia LieDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA, USA.
Jokabeth VicenteDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA, USA.
Kelsey LamDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA, USA.
Sheron GuoDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA, USA.
Jonathan ChangDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA, USA.
Violeta YuNeurological & Rare Diseases, Dewpoint Therapeutics, Boston, MA, USA.
Justin K IchidaDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA, USA; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: ichida@usc.edu.

Funding

Validating Secretory Autophagy as a Therapeutic Strategy for Diverse Forms of ALS and FTDR01NS097850 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ICHIDA, JUSTIN KAWIKA · 2016 to 2024
$5.5M
Investigation of Mechanosensory Signaling in the Pathogenesis of Traumatic Brain Injury in Human iPSC-derived Cortical Brain OrganoidsF31NS117075 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BERLIND, JOSHUA · 2021 to 2023
$135k
NINDS NIH HHS F31 NS117075NINDS NIH HHS R01 NS097850
6 · The paper itself

Abstract

Excitotoxicity is a major pathologic mechanism in patients with tauopathy and other neurodegenerative diseases. However, the key neurotoxic drivers and the most effective strategies for mitigating these degenerative processes are unclear. Here, we show that glutamate treatment of induced pluripotent stem cell (iPSC)-derived cerebral organoids induces tau oligomerization and neurodegeneration and that these phenotypes are enhanced in organoids derived from tauopathy patients. Using a genome-wide CRISPR interference (CRISPRi) screen, we find that the suppression of KCTD20 potently ameliorates tau pathology and neurodegeneration in glutamate-treated organoids and mice, as well as in transgenic mice overexpressing mutant human tau. KCTD20 suppression reduces oligomeric tau and improves neuron survival by activating lysosomal exocytosis, which clears pathological tau. Our results show that glutamate signaling can induce neuronal tau pathology and identify KCTD20 suppression and lysosomal exocytosis as effective strategies for clearing neurotoxic tau species.

Indexed as

OrganoidsTauopathiesAnimalsExocytosisGlutamic AcidHumansInduced Pluripotent Stem CellsLysosomesMiceMice, TransgenicNeuronstau ProteinsGlutamic Acidtau ProteinsexcitotoxicityFTDneurodegenerationorganoid

Identifiers

PMID40049159
PMCPMC12005969

What Socratic holds

Textmetadata
LicenceTDM
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.