Evidence map›Paper›PMID 29729668›Full record

ArticleJournal of neuroinflammation2018

URMC-099 facilitates amyloid-β clearance in a murine model of Alzheimer's disease.

Tomomi Kiyota, Jatin Machhi, Yaman Lu, Bhagyalaxmi Dyavarshetty, Maryam Nemati, Gang Zhang, R Lee Mosley, Harris A Gelbard, Howard E Gendelman

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing 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

30 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Immune senescence in aged APP/PS1 mice.NeuroImmune pharmacology and therapeutics · 2023
    Article
  10. Article
  11. Review
  12. URMC-099 prophylaxis prevents hippocampal vascular vulnerability and synaptic damage in an orthopedic model of delirium superimposed on dementia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Epigenetic Regulation of Neuroinflammation in Parkinson's Disease.International journal of molecular sciences · 2021
    Review
  18. Article
  19. Review
  20. The role of RAGE in host pathology and crosstalk between RAGE and TLR4 in innate immune signal transduction pathways.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    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.

Tomomi KiyotaDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Jatin MachhiDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Yaman LuDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Bhagyalaxmi DyavarshettyDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Maryam NematiDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Gang ZhangDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
R Lee MosleyDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Harris A GelbardCenter for Neurotherapeutics Discovery, School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY, USA.
Howard E GendelmanDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA. hegendel@unmc.edu.

Funding

Therapeutics Core (Page 286)P30MH062261 · NIMH · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI GENDELMAN, HOWARD E · 2000 to 2021
$37.7M
Targeted Neuro Protection of HIV-1 Associated Neurologic DiseaseP01MH064570 · NIMH · UNIVERSITY OF ROCHESTER · PI GELBARD, HARRIS A · 2001 to 2014
$19.4M
Pharmacokinetics and Drug-Drug InteractionsP01DA028555 · NIDA · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ALNOUTI, YAZEN · 2010 to 2019
$16.8M
Neuroprotective Immunity and HIV DementiaR01NS034239 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Howard E Gendelman, R Lee Mosley · 1995 to 2026
$12.3M
Proteomics CoreP01NS043985 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ZHENG, JIALIN CHARLES · 2003 to 2012
$11.8M
Nanomedicine and NeuroAIDSR01NS036126 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI GENDELMAN, HOWARD E · 1997 to 2017
$5.7M
Novel Kinase and Nanoformulated Protease Inhibitors for Eradication of CNS HIV-1R01MH104147 · NIMH · UNIVERSITY OF ROCHESTER · PI GELBARD, HARRIS A · 2014 to 2018
$3.2M
SMART HANDR01AG043540 · NIA · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI GENDELMAN, HOWARD E, POLUEKTOVA, LARISA Y · 2013 to 2017
$3.1M
Blood Brain Barrier Physiology and HIV DementiaR37NS036126 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI GENDELMAN, HOWARD E. · 2001 to 2007
$2.7M
Defense Advanced Research Projects Agency 421-20-09ANIA NIH HHS AG043540NIA NIH HHS R01 AG043540NIDA NIH HHS DA028555NIDA NIH HHS P01 DA028555NIMH NIH HHS MH062261NIMH NIH HHS MH064570NIMH NIH HHS P01 MH064570NIMH NIH HHS P30 MH062261NIMH NIH HHS R01 MH104147NINDS NIH HHS NS034239NINDS NIH HHS NS036126NINDS NIH HHS NS043985NINDS NIH HHS P01 NS043985NINDS NIH HHS R01 NS034239NINDS NIH HHS R01 NS036126NINDS NIH HHS R37 NS036126
6 · The paper itself

Abstract

backgroundThe mixed lineage kinase type 3 inhibitor URMC-099 facilitates amyloid-beta (Aβ) clearance and degradation in cultured murine microglia. One putative mechanism is an effect of URMC-099 on Aβ uptake and degradation. As URMC-099 promotes endolysosomal protein trafficking and reduces Aβ microglial pro-inflammatory activities, we assessed whether these responses affect Aβ pathobiogenesis. To this end, URMC-099's therapeutic potential, in Aβ precursor protein/presenilin-1 (APP/PS1) double-transgenic mice, was investigated in this model of Alzheimer's disease (AD).

methodsFour-month-old APP/PS1 mice were administered intraperitoneal URMC-099 injections at 10 mg/kg daily for 3 weeks. Brain tissues were examined by biochemical, molecular and immunohistochemical tests.

resultsURMC-099 inhibited mitogen-activated protein kinase 3/4-mediated activation and attenuated β-amyloidosis. Microglial nitric oxide synthase-2 and arginase-1 were co-localized with lysosomal-associated membrane protein 1 (Lamp1) and Aβ. Importatly, URMC-099 restored synaptic integrity and hippocampal neurogenesis in APP/PS1 mice.

conclusionsURMC-099 facilitates Aβ clearance in the brain of APP/PS1 mice. The multifaceted immune modulatory and neuroprotective roles of URMC-099 make it an attractive candidate for ameliorating the course of AD. This is buttressed by removal of pathologic Aβ species and restoration of the brain's microenvironment during disease.

Indexed as

Disease Models, AnimalAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsCells, CulturedHippocampusHumansMiceMice, TransgenicPresenilin-1Protein Kinase InhibitorsPyridinesPyrrolesAmyloid beta-PeptidesAmyloid beta-Protein PrecursorPresenilin-1Protein Kinase InhibitorsPyridinesPyrrolesURMC-099

Identifiers

PMID29729668
PMCPMC5935963

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Registered trials

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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.