COVID-19, ferrosenescence and neurodegeneration, a mini-review

Sfera, Adonis; Osorio, Carolina; Maguire, Gerald A.; Rahman, Leah; Jafri, Afzaal; Cummings, Michael; Maldonado, Jose Campo

doi:10.1016/j.pnpbp.2020.110230

Cited by 19 publications

(21 citation statements)

References 140 publications

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“…We recently reviewed the scientific literature that elucidates the impact of cellular senescence on COVID-19 complications [1]. Recent studies have discussed the association of cellular senescence in COVID-19 patients with neurodegenerative diseases [2][3][4][5]. Therefore, in the present study, we extend this scientific synopsis to comment on how cellular senescence can promote neurodegenerative diseases and to describe suitable targets for eliminating cellular senescence.…”

mentioning

confidence: 89%

Impact of Cellular Senescence on Neurodegenerative Diseases during the COVID-19 Pandemic: Sui table Targets Required to Eliminate Cellular Senescence

2021

Journal of Experimental Neurology

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mentioning

confidence: 89%

Impact of Cellular Senescence on Neurodegenerative Diseases during the COVID-19 Pandemic: Sui table Targets Required to Eliminate Cellular Senescence

2021

Journal of Experimental Neurology

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“…In our previous work, we discussed ANG II-mediated mitochondrial dysfunction and premature EC senescence (Sfera et al, 2020(Sfera et al, , 2021a. Here, based on the SARS-CoV-2 interactome, we go a step further, linking PTSD vulnerability to virus-exploited furin, Sigma-1 receptors (Sig-1Rs), plasmin, bromodomains and mitochondria, moving from specific pathways to organelle structure.…”

Section: Introductionmentioning

confidence: 95%

PTSD as an Endothelial Disease: Insights From COVID-19

Sfera

Osorio

Rahman

et al. 2021

Front. Cell. Neurosci.

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Graphical Abstract 1Covid-19 triggers endothelial cell (EC) senescence and dysfunction, likely predisposing to PTSD by increasing microvascular permeability that enables the extravasation of stress molecules into the brain trauma-processing networks in amygdala, hippocampus and the medial prefrontal cortex. The virus upregulates host angiotensin II (ANG II) (via S1 antigen), usurps furin/plasmin (via S2 antigen), mitochondria (via ORF9b), and Sigma-1 receptors (Sig-1Rs) via NSP6. These structures, previously associated with PTSD, link the SARS-CoV-2 virus to increased susceptibility for stress related disorders. As ECs are major producers of brain derived neurotrophic factor (BDNF), a neurotrophin altered in PTSD, senescent ECs lower this molecule further, predisposing to stress related disorders.

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“…young, or apparently healthy subjects) complicated infection. 1,308,309 Environmental factors have equally been called into question as possible disruptors in the course of this infection. In the past years a number of articles have evidenced in animals and humans the possible role of EMF on the dysfunctional pathways of VGCC, on peroxynitrite formation, oxidative stress and on other biochemical pathways at the root of cation dysmetabolism.…”

Section: G) Hemoglobin Hemementioning

confidence: 99%

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

et al. 2022

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Background: iron and calcium dysmetabolism, with hyperferritinemia, hypoferremia, hypocalcemia and anemia have been documented in the majority of COVID-19 patients at later/worse stages. Furthermore, complementary to ACE2, both sialic acid (SA) molecules and CD147 proved relevant host receptors for SARS-CoV-2 entry, which explains the viral attack to multiple types of cells, including erythrocytes, endothelium and neural tissue. Several authors advocated that cell ferroptosis may be the core and final cell degenerative mechanism. Methods: a literature research was performed in several scientific search engines, such as PubMed Central, Cochrane Library, Chemical Abstract Service. More than 500 articles were retrieved until mid-December 2021, to highlight the available evidence about the investigated issues. Results: based on COVID-19 literature data, we have highlighted a few pathophysiological mechanisms, associated with virus-based cation dysmetabolism, multi-organ attack, mitochondria degeneration and ferroptosis. Our suggested elucidated pathological sequence is: a) spike protein subunit S1 docking with sialylated membrane glycoproteins/receptors (ACE2, CD147), and S2 subunit fusion with the lipid layer; b) cell membrane morpho-functional changes due to the consequent electro-chemical variations and viroporin action, which induce an altered ion channel function and intracellular cation accumulation; c) additional intracellular iron concentration due to a deregulated hepcidin-ferroportin axis, with higher hepcidin levels. Viral invasion may also affect erythrocytes/erythroid precursors, endothelial cells and macrophages, through SA and CD147 receptors, with relative hemoglobin and iron/calcium dysmetabolism. AB0 blood group, hemochromatosis, or environmental elements may represent possible factors which affect individual susceptibility to COVID-19. Conclusions: our literature analysis confirms the combined role of SA molecules, ACE2, CD147, viroporins and hepcidin in determining the cation dysmetabolism and final ferroptosis in the cells infected by SARS-CoV-2. The altered ion channels and electrochemical gradients of the cell membrane have a pivotal role in the virus entry and cell dysmetabolism, with subsequent multi-organ immune-inflammatory degeneration and erythrocyte/hemoglobin alterations.

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COVID-19, ferrosenescence and neurodegeneration, a mini-review

Cited by 19 publications

References 140 publications

Impact of Cellular Senescence on Neurodegenerative Diseases during the COVID-19 Pandemic: Sui table Targets Required to Eliminate Cellular Senescence

Impact of Cellular Senescence on Neurodegenerative Diseases during the COVID-19 Pandemic: Sui table Targets Required to Eliminate Cellular Senescence

PTSD as an Endothelial Disease: Insights From COVID-19

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

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