Up-regulated Pro-inflammatory MicroRNAs (miRNAs) in Alzheimer’s disease (AD) and Age-Related Macular Degeneration (AMD)
Open accessAbstract
Alzheimer's disease (AD) of the brain neocortex and age-related macular degeneration (AMD) of the retina are two complex neurodegenerative disorders, which (i) involve the progressive dysregulation and deterioration of multiple neurobiological signaling pathways, (ii) exhibit the temporal accumulation of pro-inflammatory lesions including the amyloid beta (Aβ) peptide-containing senile plaques of AD and the drusen of AMD, and (iii) culminate in an insidious inflammatory neurodegeneration ending, respectively, in neural cell atrophy and death and progressive loss of cognition and central visual function. Recent independent research studies have indicated that AD and AMD share common, pathological signaling defects and disease mechanisms at the molecular genetic level. Using high-integrity total RNA samples pooled from AD brain and AMD retina, microfluidic hybridization miRNA arrays, and bioinformatics, the current study was undertaken to quantify microRNA (miRNA) speciation and complexity common to both AD and AMD. These small non-coding (sncRNAs) are known to post-transcriptionally regulate multiple neurobiological pathways and an abundance of research information has already been generated on the roles of these miRNAs in pathological situations involving inflammatory neuropathology and neural cell decline. Here, for the first time, we report the sequence and abundance of a septet of sncRNAs including miRNA-7, miRNA-9-1, miRNA-23a/miRNA-27a, miRNA-34a, miRNA-125b-1, miRNA-146a, and miRNA-155 that are significantly increased in abundance and common to both AD-affected superior temporal lobe neocortex (Brodmann A22) and the AMD-affected macular region of the retina. Bioinformatics, miRNA-mRNA complementarity, next-gen RNA sequencing, and feature alignment analysis further indicate that these 7 up-regulated miRNAs have the potential to interact with and down-regulate ~ 9460 target messenger RNAs (mRNAs; about 3.5% of the genome) involved in the synchronization of amyloid production and clearance, phagocytosis, innate-immune, pro-inflammatory, and neurotrophic signaling and/or synaptogenesis in diseased tissues.
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Elevated miRNA-7 levels can downregulate expression of genes involved in Aβ clearance.
“and elevated miRNA-7 levels can downregulate the expression of genes involved in Aβ clearance [622]”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [622]
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- Authors
- Pogue, A. I., & Lukiw, W. J.
- Affiliations
- Louisiana State University (US)
- Corresponding author
- Lukiw, Walter J.
- ORCID
- Lukiw, Walter J.
- Venue
- Cellular and Molecular Neurobiology
- Published
- 2018-01-04
- Volume
- 38
- Issue
- 5
- Pages
- 1021-1031
- ISSN
- 0272-4340 (ISSN-L)
- 1573-6830
- PMC
- PMC11481951
- OpenAlex
- W2782487815
- Cited by
- 105
- References
- 72
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 13 · 2023: 10 · 2022: 17 · 2021: 18 · 2020: 14 · 2019: 14 · 2018: 10
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cellular and Molecular Neurobiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG18031, AG038834)
- National Eye Institute (EY006311)
- 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 › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, age-related macular degeneration, microRNA, neuroinflammation, miRNA-mRNA interactions, amyloid-beta, drusen, retina, miR-34a, miRNA-146a, miR-155, innate immunity, synaptogenesis, neurodegeneration
- MeSH terms
- Alzheimer Disease, Base Sequence, Humans, Inflammation, Macular Degeneration, Up-Regulation, Oligonucleotide Array Sequence Analysis, MicroRNAs
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