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      Neuropathies and neurological dysfunction induced by coronaviruses

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          Abstract

          During the recent years, viral epidemic due to coronaviruses, such as SARS (Severe Acute Respiratory Syndrome), Middle East Respiratory Coronavirus Syndrome (MERS), and COVID-19 (coronavirus disese-19), has become a global problem. In addition to causing cardiovascular and respiratory lethal dysfunction, these viruses can cause neurodegeneration leading to neurological disorders. Review of the current scientific literature reveals the multiple neuropathies and neuronal dysfunction associated with these viruses. Here, we review the major findings of these studies and discuss the main neurological sequels and outcomes of coronavirus infections with SARS, MERS, and COVID-19. This article analyzes and discusses the main mechanisms of coronavirus-induced neurodegeneration according to the current experimental and clinical studies. Coronaviruses can damage the nerves directly through endovascular dysfunctions thereby affecting nerve structures and synaptic connections. Coronaviruses can also induce neural cell degeneration indirectly via mitochondrial dysfunction inducing oxidative stress, inflammation, and apoptosis. Thus, coronaviruses can cause neurological disorders by inducing neurovascular dysfunction affecting nerve structures and synaptic connections, and by inducing inflammation, oxidative stress, and apoptosis. While some of these mechanisms are similar to other RNA viruses, the neurotoxic mechanisms of COVID-19, MERS, and SARS-CoV viruses are unknown and need detailed clinical and experimental studies.

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          Most cited references127

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          Is Open Access

          Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness

          Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.
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            Free radicals and antioxidants in normal physiological functions and human disease.

            Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric oxide, NO(*)) are well recognised for playing a dual role as both deleterious and beneficial species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. Overproduction of ROS (arising either from mitochondrial electron-transport chain or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA. In contrast, beneficial effects of ROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate concentrations and involve physiological roles in cellular responses to noxia, as for example in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. Ironically, various ROS-mediated actions in fact protect cells against ROS-induced oxidative stress and re-establish or maintain "redox balance" termed also "redox homeostasis". The "two-faced" character of ROS is clearly substantiated. For example, a growing body of evidence shows that ROS within cells act as secondary messengers in intracellular signalling cascades which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS and sources of free radical generation; (ii) damage to DNA, to proteins, and to lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the maintenance of cellular "redox homeostasis"; (iv) overview of ROS-induced signaling pathways; (v) role of ROS in redox regulation of normal physiological functions, as well as (vi) role of ROS in pathophysiological implications of altered redox regulation (human diseases and ageing). Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury.
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              COVID-19 and the cardiovascular system

              Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.
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                Author and article information

                Contributors
                Luis.ulloa@duke.edu
                Motaghinezhad.m@iums.ac.ir
                Journal
                J Neurovirol
                J Neurovirol
                Journal of Neurovirology
                Springer International Publishing (Cham )
                1355-0284
                1538-2443
                13 May 2021
                : 1-17
                Affiliations
                [1 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Medicinal Chemistry, Faculty of Pharmacy, , Tehran University of Medical Sciences, ; Tehran, Iran
                [2 ]GRID grid.411746.1, ISNI 0000 0004 4911 7066, Razi Drug Research Center, , Iran University of Medical Sciences, ; Tehran, Iran
                [3 ]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Center for Perioperative Organ Protection, Department of Anesthesiology, , Duke University, ; NC 27710 Durham, USA
                Article
                977
                10.1007/s13365-021-00977-x
                8117458
                33983506
                7922f322-27f1-473e-813c-27b9b95e3dfa
                © Journal of NeuroVirology, Inc. 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 1 September 2020
                : 23 January 2021
                : 5 April 2021
                Categories
                Review

                Microbiology & Virology
                coronavirus,neurodegeneration
                Microbiology & Virology
                coronavirus, neurodegeneration

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