Evidence map›Paper›PMID 41708330›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2026

Progressive Supranuclear Palsy PERK Haplotype B Selectively Translates DLX1 Promoting Tau Toxicity.

Christian B Lessard, Diego Rubio Rubio, Samantha Tolton, Marangelie Criado-Marrero, Sakthivel Ravi, Tristyn N Garza, John Koren, Jennifer Philips, Pritha Bagchi, Karen McFarland and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2026. 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
–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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Christian B LessardCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
Diego Rubio RubioCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
Samantha ToltonDepartment of Biochemistry & Cell Biology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts 02215.
Marangelie Criado-MarreroCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
Sakthivel RaviCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
Tristyn N GarzaCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
John KorenCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
Jennifer PhilipsCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
Pritha Bagchi, Departments of Biochemistry, Emory School of Medicine, Atlanta, Georgia 30322.
Karen McFarlandPharmacology and Chemical Biology, Emory School of Medicine, Atlanta, Georgia 30322.
Deepak ChhanganiDepartment of Neurology, University of Florida, Gainesville, Florida 32610.
Todd E GoldePharmacology and Chemical Biology, Emory School of Medicine, Atlanta, Georgia 30322.
Benoit I GiassonCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
Jada LewisCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
Paramita ChakrabartyCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
Matthew J LaVoieCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
David R BorcheltCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.ORCID 0000-0002-0813-6979
Nicholas T Seyfried, Departments of Biochemistry, Emory School of Medicine, Atlanta, Georgia 30322.
Stefan ProkopCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
Diego E Rincon-LimasCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610.
Jose F AbisambraCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida 32610 j.abisambra@ufl.edu.ORCID 0000-0001-6341-679X

Funding

Social Determinants of Health, Race/Ethnicity, and White Matter HyperintensitiesP30AG066506 · NIA · UNIVERSITY OF FLORIDA · PI Ranjan Duara, DAVID LOEWENSTEIN · 2020 to 2026
$25.6M
Contributions of tau-mediated translational dysregulation to pathogenesis and progression of fronto-temporal dementiaR01AG075900 · NIA · UNIVERSITY OF FLORIDA · PI Jose Francisco Abisambra · 2022 to 2026
$2.9M
The molecular intersection of tau, TBI, and PERKR01AG074584 · NIA · UNIVERSITY OF FLORIDA · PI ABISAMBRA, JOSE FRANCISCO · 2021 to 2025
$1.9M
PERK as a Central Mediator of Neurotoxicity in TauopathiesR01NS091329 · NINDS · UNIVERSITY OF KENTUCKY · PI ABISAMBRA, JOSE FRANCISCO · 2015 to 2019
$1.6M
Harnessing new targets and mechanisms mediating AD pathogenesisR01AG077534 · NIA · UNIVERSITY OF FLORIDA · PI Diego E Rincon-Limas · 2023 to 2026
$1.5M
Pathological Implications of the tau-RNA InteractionR21AG093972 · NIA · UNIVERSITY OF FLORIDA · PI ABISAMBRA, JOSE FRANCISCO, KOREN, JOHN · 2025 to 2025
$419k
NIA NIH HHS P30 AG066506NIA NIH HHS R01 AG074584NIA NIH HHS R01 AG075900NIA NIH HHS R01 AG077534NIA NIH HHS R21 AG093972NINDS NIH HHS R01 NS091329
6 · The paper itself

Abstract

The unfolded protein response (UPR) sensor PERK exists in haplotypes A and B. PERK-B confers increased risk for tauopathies like progressive supranuclear palsy (PSP), but the mechanisms distinguishing its function from PERK-A and contributing to its association with tauopathy remain unknown. Here, we developed a controlled cellular model for a pair-wise comparison of the two PERK haplotypes, finding their UPR functions nearly indistinguishable. Puromycin-based proteomics highlighted a subset of mRNA translation events that was permissible under the PERK-B-dependent, but not the PERK-A-dependent, UPR. One of the targets that escaped PERK-B suppression was the transcription factor DLX1, which is genetically linked to PSP risk. We found that DLX1 solubility shifted to a detergent-insoluble fraction in the human brain tissue from male and female PSP donors. Furthermore, silencing the fly homolog of DLX1 was sufficient to decrease tau-induced toxicity in vivo. Our results detail the haplotype-specific PERK-B/DLX-1 pathway as a novel driver of tau pathology in cells, flies, and likely the human brain, revealing new insights into PSP pathogenesis and potential therapeutic targets.

Indexed as

eIF-2 KinaseHomeodomain ProteinsSupranuclear Palsy, Progressivetau ProteinsTranscription FactorsAnimalsFemaleHaplotypesHumansMaleUnfolded Protein ResponseDistal-less homeobox proteinsEIF2AK3 protein, humaneIF-2 KinaseHomeodomain Proteinstau ProteinsTranscription FactorsAlzheimer's diseaseDLX1PERKprogressive supranuclear palsytau

Identifiers

PMID41708330
PMCPMC13064804

What Socratic holds

Textmetadata
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.