Evidence map›Paper›PMID 36357388›Full record

ArticleNature communications2022

Maprotiline restores ER homeostasis and rescues neurodegeneration via Histamine Receptor H1 inhibition in retinal ganglion cells.

Wei Chen, Pingting Liu, Dong Liu, Haoliang Huang, Xue Feng, Fang Fang, Liang Li, Jian Wu, Liang Liu, David E Solow-Cordero and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. MRGPRX2 Mediates Mast Cell-Induced Endometriosis Pain Through the Sensitization of Sensory Neurons via Histamine/HRH1/TRPV1 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  11. Article
  12. Article
  13. Precise Correction of theResearch (Washington, D.C.) · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

11 authors at 6 institutions in 2 countries.

Wei Chen *Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.ORCID 0000-0002-7614-4436
Pingting Liu *Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.ORCID 0000-0003-1601-2818
Dong LiuDepartment of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.ORCID 0000-0001-8941-0812
Haoliang HuangDepartment of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.
Xue FengDepartment of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.
Fang FangDepartment of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.
Liang LiDepartment of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.
Jian WuDepartment of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.
Liang LiuDepartment of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.
David E Solow-CorderoHigh-Throughput Bioscience Center, Stanford University School of Medicine, Palo Alto, CA, 94305, USA.ORCID 0000-0002-9886-5058
Yang HuDepartment of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA. huyang@stanford.edu.ORCID 0000-0002-7980-1649
Stanford University · USBeijing Tongren Hospital · CNCentral South University · CNFudan University · CNHigh Throughput Biology (United States) · USStanford Medicine · US

Funding

Stanford Vision Research CoreP30EY026877 · NEI · STANFORD UNIVERSITY · PI Jeffrey L Goldberg · 2017 to 2026
$8.0M
Elucidating Neuron-Intrinsic Molecular Mechanisms of Optic Nerve RegenerationR01EY024932 · NEI · TEMPLE UNIV OF THE COMMONWEALTH · PI Yang Hu · 2015 to 2026
$4.8M
Neuroprotection by Modulating ER Stress in GlaucomaR01EY023295 · NEI · TEMPLE UNIV OF THE COMMONWEALTH · PI HU, YANG · 2013 to 2022
$3.8M
Optineurin dysfunction induces neurodegeneration in normal tension glaucoma by a novel molecular mechanismR01EY032518 · NEI · STANFORD UNIVERSITY · PI Yang Hu · 2022 to 2026
$2.7M
Developing Novel Neuroprotective Strategies for EAE/Optic NeuritisR01EY028106 · NEI · STANFORD UNIVERSITY · PI HU, YANG · 2018 to 2021
$1.9M
NEI NIH HHS P30 EY026877NEI NIH HHS R01 EY023295NEI NIH HHS R01 EY024932NEI NIH HHS R01 EY028106NEI NIH HHS R01 EY032518
6 · The paper itself

Abstract

When the protein or calcium homeostasis of the endoplasmic reticulum (ER) is adversely altered, cells experience ER stress that leads to various diseases including neurodegeneration. Genetic deletion of an ER stress downstream effector, CHOP, significantly protects neuron somata and axons. Here we report that three tricyclic compounds identified through a small-scale high throughput screening using a CHOP promoter-driven luciferase cell-based assay, effectively inhibit ER stress by antagonizing their common target, histamine receptor H1 (HRH1). We further demonstrated that systemic administration of one of these compounds, maprotiline, or CRISPR-mediated retinal ganglion cell (RGC)-specific HRH1 inhibition, delivers considerable neuroprotection of both RGC somata and axons and preservation of visual function in two mouse optic neuropathy models. Finally, we determine that maprotiline restores ER homeostasis by inhibiting HRH1-mediated Ca

Indexed as

MaprotilineRetinal Ganglion CellsAnimalsDisease Models, AnimalEndoplasmic ReticulumEndoplasmic Reticulum StressHomeostasisMiceReceptors, HistamineMaprotilineReceptors, Histamine

Identifiers

PMID36357388
PMCPMC9649812
OpenAlexW4309076161

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.