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Cited by 49MicroRNA in disease regulationNeuroinflammation and Neurodegeneration MechanismsAcute Ischemic Stroke Management

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MiRNA: Involvement of the MAPK Pathway in Ischemic Stroke. A Promising Therapeutic Target

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Gugliandolo, Agnese, Silvestro, Serena, Sindona, Cinzia, Bramanti, Placido, Mazzon, Emanuela·2021·Medicina
DOI 10.3390/medicina57101053PMC PMC8539390
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Abstract

Ischemic stroke (IS) is a cerebrovascular disease with a high rate of disability and mortality. It is classified as the second leading cause of death that arises from the sudden occlusion of small vessels in the brain with consequent lack of oxygen and nutrients in the brain tissue. Following an acute ischemic event, the cascade of events promotes the activation of multiple signaling pathways responsible for irreversible neuronal damage. The mitogen-activated protein kinase (MAPK) signaling pathway transmits signals from the cell membrane to the nucleus in response to different stimuli, regulating proliferation, differentiation, inflammation, and apoptosis. Several lines of evidence showed that MAPK is an important regulator of ischemic and hemorrhagic cerebral vascular disease; indeed, it can impair blood–brain barrier (BBB) integrity and exacerbate neuroinflammation through the release of pro-inflammatory mediators implementing neurovascular damage after ischemic stroke. This review aims to illustrate the miRNAs involved in the regulation of MAPK in IS, in order to highlight possible targets for potential neuroprotective treatments. We also discuss some miRNAs (miR), including miR-145, miR-137, miR-493, and miR-126, that are important as they modulate processes such as apoptosis, neuroinflammation, neurogenesis, and angiogenesis through the regulation of the MAPK pathway in cerebral IS. To date, limited drug therapies are available for the treatment of IS; therefore, it is necessary to implement preclinical and clinical studies aimed at discovering novel therapeutic approaches to minimize post-stroke neurological damage.

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  • The three selected miRNAs-hsa-miR-122-5p, hsa-let-7a-5p, and hsa-miR-26a-5p-provide complementary and comprehensive coverage of almost all critical genes associated with the MAPK signaling pathway.

    “From this analysis, we selected the three abundant miRNAs-hsa-miR-122-5p, hsa-let-7a-5p, and hsa-miR26a-5p-based on their complementary and comprehensive coverage of almost all the critical genes associated with the MAPK signaling pathway 27-33 as analyzed using miRTarBase version 8.0 and TarBase v8.0 integrated within miRNet (Figure S1).”

    From rAAV-mediated Multi-miRNA Delivery Targeting MAPK Pathway Suppresses Laser-induced Choroidal Neovascularization in Mice (2026) · cites this paper as [31]

    Section 2.1 links miR-122 to MAPK signaling in ischemic stroke, and Section 2.3 links miR-26a to ERK signaling. The review does not establish that these two miRNAs and hsa-let-7a-5p together cover almost all critical MAPK-pathway genes; that coverage is described in the citing sentence as the citing authors’ own analysis. No page numbers were available in our copy. (LLM, conf=0.85)

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Metadata

Authors
Gugliandolo, A., Silvestro, S., Sindona, C., Bramanti, P., & Mazzon, E.
Affiliations
Centro Neurolesi Bonino Pulejo (IT)
Corresponding author
Mazzon, Emanuela
ORCID
Venue
Medicina
Publisher
MDPI AG
Published
2021-10-01
Volume
57
Issue
10
Pages
1053
ISSN
  • 1010-660X (ISSN-L)
  • 1648-9144
DOI
10.3390/medicina57101053
PMC
PMC8539390
OpenAlex
W3202062386
Cited by
49
References
0
Citations by year
2026: 7 · 2025: 11 · 2024: 14 · 2023: 10 · 2022: 7
FWCI
0.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Medicina (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • IRIS eCampus Telematic University (Università degli Studi eCampus) (submittedVersion)
Funders
Ministero della Salute (-)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
Keywords
ischemic stroke, microRNA, MAPK signaling, miR-145, miR-137, miR-126, neuroinflammation, blood-brain barrier integrity, apoptosis, neurogenesis, angiogenesis, neuroprotection, therapeutic target
MeSH terms
Ischemic Stroke, Brain Ischemia, Humans, Stroke, Mitogen-Activated Protein Kinases, MicroRNAs

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