Evidence map›Paper›PMID 38718909›Full record

ArticleBrain, behavior, and immunity2024

Microglia-targeted inhibition of miR-17 via mannose-coated lipid nanoparticles improves pathology and behavior in a mouse model of Alzheimer's disease.

Asmaa Badr, Kylene P Daily, Mostafa Eltobgy, Shady Estfanous, Michelle H Tan, Jimmy Chun-Tien Kuo, Owen Whitham, Cierra Carafice, Gauruv Gupta, Heba M Amer and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain, behavior, and immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

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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

24 authors.

Asmaa BadrDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Kylene P DailyDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Mostafa EltobgyDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Shady EstfanousDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Michelle H TanDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Jimmy Chun-Tien KuoDivision of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, the United States of America.
Owen WhithamDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Cierra CaraficeDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Gauruv GuptaDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Heba M AmerDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Mohamed M ShamseldinDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Amir YousifDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Nicholas P DeemsInstitute for Behavioral Medicine Research, Ohio State University, Columbus, OH, the United States of America.
Julie FitzgeraldDepartment of Neuroscience, The Ohio State University, Columbus, OH 43210.
Pearlly YanGenomics Shared Resource, Comprehensive Cancer Center, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, the United States of America.
Amy WebbDepartment of Biomedical Informatics, The Ohio State University, Columbus, OH, the United States of America.
Xiaoli ZhangDepartment of Biomedical Informatics, The Ohio State University, Columbus, OH, the United States of America.
Maciej PietrzakDepartment of Biomedical Informatics, The Ohio State University, Columbus, OH, the United States of America.
Hazem E GhoneimDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Purnima DubeyDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America.
Ruth M BarrientosInstitute for Behavioral Medicine Research, Ohio State University, Columbus, OH, the United States of America.
Robert J LeeDivision of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, the United States of America.
Olga N Kokiko-CochranDepartment of Neuroscience, The Ohio State University, Columbus, OH 43210.
Amal O AmerDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, the United States of America. Electronic address: amal.amer@osumc.edu.

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
THE ROLE OF THE NON-CANONICAL INFLAMMASOME IN INNATE IMMUNITYR01AI159452 · NIAID · OHIO STATE UNIVERSITY · PI AMER, AMAL O, SEVEAU, STEPHANIE M M · 2021 to 2025
$3.7M
Mechanisms of lung and cardiac pathology in SARS-CoV-2 infectionsR01HL168501 · NHLBI · OHIO STATE UNIVERSITY · PI Amal O Amer, Jacob Yount · 2023 to 2026
$2.9M
Targeting specific MicroRNA to alleviate Alzheimer’s Disease pathobiologyR01AG082113 · NIA · OHIO STATE UNIVERSITY · PI Amal O Amer · 2023 to 2026
$2.7M
Enhancing the Effectiveness of Immunotherapies by T Cell Epigenetic ReprogrammingR01AI170926 · NIAID · OHIO STATE UNIVERSITY · PI Hazem E. Ghoneim · 2023 to 2026
$2.6M
The role of microRNA-calibrated autophagy in innate immunity and inflammationR01HL127651 · NHLBI · OHIO STATE UNIVERSITY · PI AMER, AMAL O, CORMET-BOYAKA, ESTELLE A · 2015 to 2018
$1.5M
Alteration of bronchial epithelium host defenses by marijuana and vaping preparationsR21DA057799 · NIDA · OHIO STATE UNIVERSITY · PI CORMET-BOYAKA, ESTELLE A · 2023 to 2024
$433k
Mechanistic basis of inflammation in Alzheimers DiseaseR21AG064899 · NIA · OHIO STATE UNIVERSITY · PI AMER, AMAL O · 2020 to 2021
$409k
NCI NIH HHS P30 CA016058NHLBI NIH HHS R01 HL127651NHLBI NIH HHS R01 HL168501NIAID NIH HHS R01 AI159452NIAID NIH HHS R01 AI170926NIA NIH HHS R01 AG082113NIDA NIH HHS R21 DA057799
6 · The paper itself

Abstract

Neuroinflammation and accumulation of Amyloid Beta (Aβ) accompanied by deterioration of special memory are hallmarks of Alzheimer's disease (AD). Effective preventative and treatment options for AD are still needed. Microglia in AD brains are characterized by elevated levels of microRNA-17 (miR-17), which is accompanied by defective autophagy, Aβ accumulation, and increased inflammatory cytokine production. However, the effect of targeting miR-17 on AD pathology and memory loss is not clear. To specifically inhibit miR-17 in microglia, we generated mannose-coated lipid nanoparticles (MLNPs) enclosing miR-17 antagomir (Anti-17 MLNPs), which are targeted to mannose receptors readily expressed on microglia. We used a 5XFAD mouse model (AD) that recapitulates many AD-related phenotypes observed in humans. Our results show that Anti-17 MLNPs, delivered to 5XFAD mice by intra-cisterna magna injection, specifically deliver Anti-17 to microglia. Anti-17 MLNPs downregulated miR-17 expression in microglia but not in neurons, astrocytes, and oligodendrocytes. Anti-17 MLNPs attenuated inflammation, improved autophagy, and reduced Aβ burdens in the brains. Additionally, Anti-17 MLNPs reduced the deterioration in spatial memory and decreased anxiety-like behavior in 5XFAD mice. Therefore, targeting miR-17 using MLNPs is a viable strategy to prevent several AD pathologies. This selective targeting strategy delivers specific agents to microglia without the adverse off-target effects on other cell types. Additionally, this approach can be used to deliver other molecules to microglia and other immune cells in other organs.

Indexed as

Alzheimer DiseaseBrainDisease Models, AnimalMannoseMice, TransgenicMicrogliaMicroRNAsNanoparticlesAmyloid beta-PeptidesAnimalsAntagomirsLipidsMaleMiceAmyloid beta-PeptidesAntagomirsLipidsMannoseMicroRNAsMirn17 microRNA, mouseAlzheimer’s diseaseAmyloid betaLipid nanoparticlesMannose-coated nanoparticlesMice behaviorMicrogliaMicroRNAmiR-17NeuroinflammationRNA sequencing

Identifiers

PMID38718909
PMCPMC11781315

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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.