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Up-regulated Pro-inflammatory MicroRNAs (miRNAs) in Alzheimer's disease (AD) and Age-Related Macular Degeneration (AMD).
Cell Mol Neurobiol. 2018 Jul; 38(5):1021-1031.CM

Abstract

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.

Authors+Show Affiliations

Alchem Biotech Research, Toronto, ON, Canada.Alchem Biotech Research, Toronto, ON, Canada. wlukiw@lsuhsc.edu. Neuroscience Center, Louisiana State University School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 70112-2272, USA. wlukiw@lsuhsc.edu. Department of Neurology, Louisiana State University School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 70112-2272, USA. wlukiw@lsuhsc.edu. Department of Ophthalmology, Louisiana State University School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 70112-2272, USA. wlukiw@lsuhsc.edu. LSU Neuroscience Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite 904, New Orleans, LA, 70112-2272, USA. wlukiw@lsuhsc.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29302837

Citation

Pogue, Aileen I., and Walter J. Lukiw. "Up-regulated Pro-inflammatory MicroRNAs (miRNAs) in Alzheimer's Disease (AD) and Age-Related Macular Degeneration (AMD)." Cellular and Molecular Neurobiology, vol. 38, no. 5, 2018, pp. 1021-1031.
Pogue AI, Lukiw WJ. Up-regulated Pro-inflammatory MicroRNAs (miRNAs) in Alzheimer's disease (AD) and Age-Related Macular Degeneration (AMD). Cell Mol Neurobiol. 2018;38(5):1021-1031.
Pogue, A. I., & Lukiw, W. J. (2018). Up-regulated Pro-inflammatory MicroRNAs (miRNAs) in Alzheimer's disease (AD) and Age-Related Macular Degeneration (AMD). Cellular and Molecular Neurobiology, 38(5), 1021-1031. https://doi.org/10.1007/s10571-017-0572-3
Pogue AI, Lukiw WJ. Up-regulated Pro-inflammatory MicroRNAs (miRNAs) in Alzheimer's Disease (AD) and Age-Related Macular Degeneration (AMD). Cell Mol Neurobiol. 2018;38(5):1021-1031. PubMed PMID: 29302837.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Up-regulated Pro-inflammatory MicroRNAs (miRNAs) in Alzheimer's disease (AD) and Age-Related Macular Degeneration (AMD). AU - Pogue,Aileen I, AU - Lukiw,Walter J, Y1 - 2018/01/04/ PY - 2017/10/14/received PY - 2017/12/21/accepted PY - 2018/1/6/pubmed PY - 2018/10/6/medline PY - 2018/1/6/entrez KW - Age-related macular degeneration KW - Alzheimer’s disease KW - MicroRNA–mRNA integration KW - Neurotrophic signaling KW - Phagocytosis KW - Prion disease KW - Synaptogenesis SP - 1021 EP - 1031 JF - Cellular and molecular neurobiology JO - Cell Mol Neurobiol VL - 38 IS - 5 N2 - 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. SN - 1573-6830 UR - https://www.unboundmedicine.com/medline/citation/29302837/Up_regulated_Pro_inflammatory_MicroRNAs__miRNAs__in_Alzheimer's_disease__AD__and_Age_Related_Macular_Degeneration__AMD__ DB - PRIME DP - Unbound Medicine ER -