Editorial: Somatic genomic mosaicism &amp; human disease

Iourov, Ivan Y.; Heng, Henry H.Q.

doi:10.3389/fgene.2022.1045559

Cited by 4 publications

(1 citation statement)

References 15 publications

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“…Moreover, neuronal syncytia were demonstrated in both normal and pathological aging, suggesting that aneuploidy and polyploidy could be more common in the human brain than currently believed [ 95 , 96 ]. Indeed, somatic mosaicism (genomic differences from neuron to neuron) was discovered with the help of a new technique capable of discerning chromosomes in individual cells [ 97 ]. The fact that neurons have different DNA from one cell to another is significant and may be the result of genome reorganization after viral infections or TE mobilization.…”

Section: Fusion Of Postmitotic Cells: Heart and Brain Syncytiamentioning

confidence: 99%

Long COVID as a Tauopathy: Of “Brain Fog” and “Fusogen Storms”

Sfera

Rahman

Campo

et al. 2023

IJMS

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Long COVID, also called post-acute sequelae of SARS-CoV-2, is characterized by a multitude of lingering symptoms, including impaired cognition, that can last for many months. This symptom, often called “brain fog”, affects the life quality of numerous individuals, increasing medical complications as well as healthcare expenditures. The etiopathogenesis of SARS-CoV-2-induced cognitive deficit is unclear, but the most likely cause is chronic inflammation maintained by a viral remnant thriving in select body reservoirs. These viral sanctuaries are likely comprised of fused, senescent cells, including microglia and astrocytes, that the pathogen can convert into neurotoxic phenotypes. Moreover, as the enteric nervous system contains neurons and glia, the virus likely lingers in the gastrointestinal tract as well, accounting for the intestinal symptoms of long COVID. Fusogens are proteins that can overcome the repulsive forces between cell membranes, allowing the virus to coalesce with host cells and enter the cytoplasm. In the intracellular compartment, the pathogen hijacks the actin cytoskeleton, fusing host cells with each other and engendering pathological syncytia. Cell–cell fusion enables the virus to infect the healthy neighboring cells. We surmise that syncytia formation drives cognitive impairment by facilitating the “seeding” of hyperphosphorylated Tau, documented in COVID-19. In our previous work, we hypothesized that the SARS-CoV-2 virus induces premature endothelial senescence, increasing the permeability of the intestinal and blood–brain barrier. This enables the migration of gastrointestinal tract microbes and/or their components into the host circulation, eventually reaching the brain where they may induce cognitive dysfunction. For example, translocated lipopolysaccharides or microbial DNA can induce Tau hyperphosphorylation, likely accounting for memory problems. In this perspective article, we examine the pathogenetic mechanisms and potential biomarkers of long COVID, including microbial cell-free DNA, interleukin 22, and phosphorylated Tau, as well as the beneficial effect of transcutaneous vagal nerve stimulation.

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Section: Fusion Of Postmitotic Cells: Heart and Brain Syncytiamentioning

confidence: 99%