Fission Impossible: Stabilized miRNA-Based Analogs in Neurodegenerative Disease

Lukiw, Walter J.

doi:10.3389/fnins.2022.875957

Cited by 5 publications

(13 citation statements)

References 65 publications

(156 reference statements)

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“…Therefore, medical advances during the COVID-19 pandemic could incidentally improve general health worldwide. Very interestingly, miR146a-5p is also involved in aging, cardiovascular and metabolic diseases, cancers, autoimmune diseases such as rheumatoid arthritis [ 97 ] or multiple sclerosis [ 98 ], and neurodegenerative diseases [ 99 ]. Likewise, HRV is also a prognostic factor in several non-infectious diseases [ 100 ].…”

Section: Discussion: Novel Therapies Targeting Vagus Nerve Stimulatio...mentioning

confidence: 99%

Understanding the Pivotal Role of the Vagus Nerve in Health from Pandemics

Rangon¹,

Niezgoda

2022

Bioengineering

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The COVID-19 pandemic seems endless with the regular emergence of new variants. Is the SARS-CoV-2 virus particularly evasive to the immune system, or is it merely disrupting communication between the body and the brain, thus pre-empting homeostasis? Retrospective analysis of the COVID-19 and AIDS pandemics, as well as prion disease, emphasizes the pivotal but little-known role of the 10th cranial nerve in health. Considering neuroimmunometabolism from the point of view of the vagus nerve, non-invasive bioengineering solutions aiming at monitoring and stimulating the vagal tone are subsequently discussed as the next optimal and global preventive treatments, far beyond pandemics.

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Section: Discussion: Novel Therapies Targeting Vagus Nerve Stimulatio...mentioning

confidence: 99%

Understanding the Pivotal Role of the Vagus Nerve in Health from Pandemics

Rangon¹,

Niezgoda

2022

Bioengineering

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“…Almost 50 years ago, the two-time Nobel laureate, Linus Pauling, first described the significant biological variation in genotypic versus phenotypic parameters among human individuals, based in part on studies from hemoglobin genetics [ 42 , 43 , 44 , 45 , 46 , 47 ]. Overall, this concept has come to be known as “ human biochemical individuality ” [ 43 , 44 , 45 , 46 ].…”

Section: Human Biochemical Individuality—why Not All Covid-19 Patient...mentioning

confidence: 99%

Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain

Lukiw

Pogue²

2023

IJMS

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The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m7GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue type, in silico analysis, RNA sequencing, and molecular-genetic investigations indicate that, remarkably, almost every single human miRNA has the potential to interact with the primary sequence of SARS-CoV-2 ssvRNA. Individual human variation in host miRNA abundance, speciation, and complexity among different human populations and additional variability in the cell and tissue distribution of the SARS-CoV-2 angiotensin converting enzyme-2 (ACE2) receptor (ACE2R) appear to further contribute to the molecular-genetic basis for the wide variation in individual host cell and tissue susceptibility to COVID-19 infection. In this paper, we review recently described aspects of the miRNA and ssvRNA ribonucleotide sequence structure in this highly evolved miRNA–ssvRNA recognition and signaling system and, for the first time, report the most abundant miRNAs in the control superior temporal lobe neocortex (STLN), an anatomical area involved in cognition and targeted by both SARS-CoV-2 invasion and Alzheimer’s disease (AD). We further evaluate important factors involving the neurotropic nature of SARS-CoV-2 and miRNAs and ACE2R distribution in the STLN that modulate significant functional deficits in the brain and CNS associated with SARS-CoV-2 infection and COVID-19’s long-term neurological effects.

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“…Abundant evidence has accumulated that circRNAs possess several biological functions including miRNA sponging, roles in transcriptional regulation, the specific splicing of heterogeneous nuclear RNA (hnRNA) and have capability to act as polypeptide-generating templates (Zhao et al, 2016;Lauretti et al, 2021;Nisar et al, 2021;Rybak-Wolf and Plass 2021;Sharma et al, 2022;Sinha et al, 2022;Wang et al, 2022;Zhang et al, 2022). Emerging data further indicates that circRNAs play important and determinant roles in both health and disease ranging from acute CNS injuries including ischemic stroke and traumatic brain injury to cancer and AD (Salzman et al, 2012;Hansen et al, 2013;Memczak et al, 2013;Lukiw 2022;Sharma et al, 2022;Sinha et al, 2022;Zhang et al, 2022). Although circRNAs may take many forms that include coding and non-coding RNA (ncRNA) sequences and vary widely in individual abundance, speciation, size and complexity this current paper will focus on circRNAs containing miRNA-and anti-miRNA-type regulatory sequences for which a relatively large amount of basic research has already been completed.…”

Section: Overviewmentioning

confidence: 99%

“…Global miRNA and mRNA expression patterns for specific anatomical regions of the brain and CNS have already been established for AD at various stages of disease in defined groups of AD patients (Lukiw et al, 1992;Colangelo et al, 2002;Burmistrova et al, 2007;Lukiw 2007;Lukiw 2007;Cogswell et al, 2008;Sethi and Lukiw 2009;Ginsberg et al, 2012;Wilusz and Sharp 2013;Bhattacharjee et al, 2016;Zhao et al, 2016;Jaber et al, 2017;Millan et al, 2017;Pogue and Lukiw 2018;Jaber et al, 2019;Sarkar et al, 2019;Zhao et al, 2020;Lauretti et al, 2021;Nguyen et al, 2021;Rybak-Wolf and Plass 2021;Tasker et al, 2021;Walgrave et al, 2021;Wei et al, 2020;Lukiw 2022;Pogue et al, 2022;Roy et al, 2022;Yoon et al, 2022). This wealth of genetic and epigenetic information could be used as a guide to initially address and correct dysregulated miRNA patterns in the AD brain using specifically engineered circRNA.…”

Section: Mirna Abundance Complexity and Speciation In Admentioning

confidence: 99%

“…As few as 10 NF-kB-sensitive miRNAs or clustered miRNA families up-regulated in abundance in AD hippocampus, including can explain most of the major features of AD neuropathology in the limbic regions of multiple AD patients. These involve functionally interactive molecular networks implicated in amyloid and neurofibrillary homeostasis, amyloidogenesis, altered NF-kB (p50/p65) and innate-immune signaling, tau pathology, deficits in phagocytosis, catabolism, neurotrophism, synaptogenesis and/ or neuro-inflammation (Lukiw, 2007;Millan, 2017;Pogue and Lukiw, 2018;Brennan and Henshall, 2020;Wei et al, 2020;Nguyen et al, 2021;Tasker et al, 2021;Walgrave et al, 2021;Lukiw 2022). As an initial guide, a circRNA containing AM sequences to the above mentioned 10-member pathological miRNA family could be synthesized to stabilize these altered miRNA levels.…”

Section: Mirna Abundance Complexity and Speciation In Admentioning

confidence: 99%

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