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1.
Cell Mol Biol Lett ; 27(1): 10, 2022 Feb 02.
Article in English | MEDLINE | ID: covidwho-1753103

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and finding a safe therapeutic strategy and effective vaccine is critical to overcoming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, elucidation of pathogenesis mechanisms, especially entry routes of SARS-CoV-2 may help propose antiviral drugs and novel vaccines. Several receptors have been demonstrated for the interaction of spike (S) protein of SARS-CoV-2 with host cells, including angiotensin-converting enzyme (ACE2), ephrin ligands and Eph receptors, neuropilin 1 (NRP-1), P2X7, and CD147. The expression of these entry receptors in the central nervous system (CNS) may make the CNS prone to SARS-CoV-2 invasion, leading to neurodegenerative diseases. The present review provides potential pathological mechanisms of SARS-CoV-2 infection in the CNS, including entry receptors and cytokines involved in neuroinflammatory conditions. Moreover, it explains several neurodegenerative disorders associated with COVID-19. Finally, we suggest inflammasome and JaK inhibitors as potential therapeutic strategies for neurodegenerative diseases.


Subject(s)
COVID-19/drug therapy , Central Nervous System/drug effects , Inflammasomes/drug effects , Neurodegenerative Diseases/drug therapy , Receptors, Virus/genetics , SARS-CoV-2/drug effects , Virus Internalization/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/therapeutic use , Basigin/genetics , Basigin/metabolism , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , Central Nervous System/metabolism , Central Nervous System/virology , Ephrins/genetics , Ephrins/metabolism , Gene Expression Regulation , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Humans , Immunologic Factors/therapeutic use , Inflammasomes/genetics , Inflammasomes/metabolism , Janus Kinase Inhibitors/therapeutic use , Janus Kinases/antagonists & inhibitors , Janus Kinases/genetics , Janus Kinases/metabolism , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/virology , Neuropilin-1/genetics , Neuropilin-1/metabolism , Receptors, Purinergic P2X7/genetics , Receptors, Purinergic P2X7/metabolism , Receptors, Virus/antagonists & inhibitors , Receptors, Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Signal Transduction
2.
Int J Biol Macromol ; 193(Pt A): 838-846, 2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1487745

ABSTRACT

Discovery of robust, selective and specific biomarkers are important for early diagnosis and monitor progression of human diseases. Eye being a common target for several human diseases, vision impediment and complications are often associated with systemic and ocular diseases. Tears are bodily fluids that are closest to eye and are rich in protein content and other metabolites. As a biomarker repository, it advantages over other bodily fluids due to the ability to collect it non-invasively. In this review, we highlight some recent advancements in identification of tear-based protein biomarkers like lacryglobin and cystatin SA for cancer; interleukin-6 and immunoglobulin-A antibody for COVID-19; tau, amyloid-ß-42 and lysozyme-C for Alzheimer's disease; peroxiredoxin-6 and α-synuclein for Parkinson's disease; kallikrein, angiotensin converting enzyme and lipocalin-1 for glaucoma; lactotransferrin and lipophilin-A for diabetic retinopathy and zinc-alpha-2 glycoprotein-1, prolactin and calcium binding protein-A4 for eye thyroid disease. We also discussed identification of tear based non-protein biomarkers like lysophospholipids and acetylcarnitine for glaucoma, 8-hydroxy-2'-deoxyquanosine and malondialdehyde for thyroid eye disease. We elucidate technological advancement in developing tear-based biosensors for diagnosis and monitoring diseases such as diabetes, diabetic retinopathy and Alzheimer's disease. Altogether, the study of tears as potential biomarkers for early diagnosis of human diseases is promising.


Subject(s)
Biomarkers, Tumor/metabolism , COVID-19 , Early Detection of Cancer , Eye Diseases , Neurodegenerative Diseases , SARS-CoV-2/metabolism , Tears/metabolism , COVID-19/diagnosis , COVID-19/metabolism , Eye Diseases/diagnosis , Eye Diseases/metabolism , Humans , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/metabolism
4.
Adv Food Nutr Res ; 96: 251-310, 2021.
Article in English | MEDLINE | ID: covidwho-1240122

ABSTRACT

Since the discovery of manifest Zn deficiency in 1961, the increasing number of studies demonstrated the association between altered Zn status and multiple diseases. In this chapter, we provide a review of the most recent advances on the role of Zn in health and disease (2010-20), with a special focus on the role of Zn in neurodegenerative and neurodevelopmental disorders, diabetes and obesity, male and female reproduction, as well as COVID-19. In parallel with the revealed tight association between ASD risk and severity and Zn status, the particular mechanisms linking Zn2+ and ASD pathogenesis like modulation of synaptic plasticity through ProSAP/Shank scaffold, neurotransmitter metabolism, and gut microbiota, have been elucidated. The increasing body of data indicate the potential involvement of Zn2+ metabolism in neurodegeneration. Systemic Zn levels in Alzheimer's and Parkinson's disease were found to be reduced, whereas its sequestration in brain may result in modulation of amyloid ß and α-synuclein processing with subsequent toxic effects. Zn2+ was shown to possess adipotropic effects through the role of zinc transporters, zinc finger proteins, and Zn-α2-glycoprotein in adipose tissue physiology, underlying its particular role in pathogenesis of obesity and diabetes mellitus type 2. Recent findings also contribute to further understanding of the role of Zn2+ in spermatogenesis and sperm functioning, as well as oocyte development and fertilization. Finally, Zn2+ was shown to be the potential adjuvant therapy in management of novel coronavirus infection (COVID-19), underlining the perspectives of zinc in management of old and new threats.


Subject(s)
Autism Spectrum Disorder/metabolism , COVID-19/metabolism , Diabetes Mellitus, Type 2/metabolism , Neurodegenerative Diseases/metabolism , Obesity/metabolism , Reproduction , Zinc/metabolism , Alzheimer Disease/metabolism , Animals , COVID-19/drug therapy , Female , Humans , Male , Neurodevelopmental Disorders/metabolism , Nutritional Status , Parkinson Disease/metabolism , Zinc/deficiency , Zinc/therapeutic use
5.
Brain ; 144(10): 2915-2932, 2021 11 29.
Article in English | MEDLINE | ID: covidwho-1238183

ABSTRACT

Neurodegenerative proteinopathies are characterized by progressive cell loss that is preceded by the mislocalization and aberrant accumulation of proteins prone to aggregation. Despite their different physiological functions, disease-related proteins like tau, α-synuclein, TAR DNA binding protein-43, fused in sarcoma and mutant huntingtin, all share low complexity regions that can mediate their liquid-liquid phase transitions. The proteins' phase transitions can range from native monomers to soluble oligomers, liquid droplets and further to irreversible, often-mislocalized aggregates that characterize the stages and severity of neurodegenerative diseases. Recent advances into the underlying pathogenic mechanisms have associated mislocalization and aberrant accumulation of disease-related proteins with defective nucleocytoplasmic transport and its mediators called karyopherins. These studies identify karyopherin abnormalities in amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer's disease, and synucleinopathies including Parkinson's disease and dementia with Lewy bodies, that range from altered expression levels to the subcellular mislocalization and aggregation of karyopherin α and ß proteins. The reported findings reveal that in addition to their classical function in nuclear import and export, karyopherins can also act as chaperones by shielding aggregation-prone proteins against misfolding, accumulation and irreversible phase-transition into insoluble aggregates. Karyopherin abnormalities can, therefore, be both the cause and consequence of protein mislocalization and aggregate formation in degenerative proteinopathies. The resulting vicious feedback cycle of karyopherin pathology and proteinopathy identifies karyopherin abnormalities as a common denominator of onset and progression of neurodegenerative disease. Pharmacological targeting of karyopherins, already in clinical trials as therapeutic intervention targeting cancers such as glioblastoma and viral infections like COVID-19, may therefore represent a promising new avenue for disease-modifying treatments in neurodegenerative proteinopathies.


Subject(s)
Karyopherins/metabolism , Neurodegenerative Diseases/metabolism , Proteostasis Deficiencies/metabolism , Animals , Brain/drug effects , Brain/metabolism , Humans , Karyopherins/genetics , Neurodegenerative Diseases/drug therapy , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Proteostasis Deficiencies/drug therapy
6.
Biochem Biophys Res Commun ; 554: 94-98, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1157142

ABSTRACT

The post-infection of COVID-19 includes a myriad of neurologic symptoms including neurodegeneration. Protein aggregation in brain can be considered as one of the important reasons behind the neurodegeneration. SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) binds to heparin and heparin binding proteins. Moreover, heparin binding accelerates the aggregation of the pathological amyloid proteins present in the brain. In this paper, we have shown that the SARS-CoV-2 S1 RBD binds to a number of aggregation-prone, heparin binding proteins including Aß, α-synuclein, tau, prion, and TDP-43 RRM. These interactions suggests that the heparin-binding site on the S1 protein might assist the binding of amyloid proteins to the viral surface and thus could initiate aggregation of these proteins and finally leads to neurodegeneration in brain. The results will help us to prevent future outcomes of neurodegeneration by targeting this binding and aggregation process.


Subject(s)
Amyloid/metabolism , COVID-19/metabolism , Heparin/metabolism , Neurodegenerative Diseases/metabolism , Protein Aggregation, Pathological , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , Amyloid beta-Peptides/metabolism , Brain/metabolism , Brain/pathology , Brain/virology , COVID-19/virology , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/metabolism , Humans , Molecular Docking Simulation , Neurodegenerative Diseases/virology , Prions/metabolism , Protein Binding , SARS-CoV-2/chemistry , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , alpha-Synuclein/metabolism , tau Proteins/metabolism
7.
Int J Mol Sci ; 22(4)2021 Feb 18.
Article in English | MEDLINE | ID: covidwho-1110432

ABSTRACT

The mitochondrial respiratory chain is the main site of reactive oxygen species (ROS) production in the cell. Although mitochondria possess a powerful antioxidant system, an excess of ROS cannot be completely neutralized and cumulative oxidative damage may lead to decreasing mitochondrial efficiency in energy production, as well as an increasing ROS excess, which is known to cause a critical imbalance in antioxidant/oxidant mechanisms and a "vicious circle" in mitochondrial injury. Due to insufficient energy production, chronic exposure to ROS overproduction consequently leads to the oxidative damage of life-important biomolecules, including nucleic acids, proteins, lipids, and amino acids, among others. Different forms of mitochondrial dysfunction (mitochondriopathies) may affect the brain, heart, peripheral nervous and endocrine systems, eyes, ears, gut, and kidney, among other organs. Consequently, mitochondriopathies have been proposed as an attractive diagnostic target to be investigated in any patient with unexplained progressive multisystem disorder. This review article highlights the pathomechanisms of mitochondriopathies, details advanced analytical tools, and suggests predictive approaches, targeted prevention and personalization of medical services as instrumental for the overall management of mitochondriopathy-related cascading pathologies.


Subject(s)
Energy Metabolism , Mitochondria/pathology , Mitochondrial Diseases/pathology , Oxidative Stress , Animals , Carcinogenesis/pathology , Humans , Mitochondria/metabolism , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/metabolism , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Precision Medicine , Reactive Oxygen Species/metabolism
8.
Cells ; 10(2)2021 02 16.
Article in English | MEDLINE | ID: covidwho-1106076

ABSTRACT

Parkinson's disease (PD) is the second most common neurodegenerative disease, afflicting ~10 million people worldwide. Although several genes linked to PD are currently identified, PD remains primarily an idiopathic disorder. Neuronal protein α-synuclein is a major player in disease progression of both genetic and idiopathic forms of PD. However, it cannot alone explain underlying pathological processes. Recent studies demonstrate that many other risk factors can accelerate or further worsen brain dysfunction in PD patients. Several PD models, including non-mammalian eukaryotic organisms, have been developed to identify and characterize these factors. This review discusses recent findings in three PD model organisms, i.e., yeast, Drosophila, and Caenorhabditis elegans, that opened new mechanisms and identified novel contributors to this disorder. These non-mammalian models share many conserved molecular pathways and cellular processes with humans. New players affecting PD pathogenesis include previously unknown genes/proteins, novel signaling pathways, and low molecular weight substances. These findings might respond to the urgent need to discover novel drug targets for PD treatment and new biomarkers for early diagnostics of this disease. Since the study of neurodegeneration using simple eukaryotic organisms brought a huge amount of information, we include only the most recent or the most important relevant data.


Subject(s)
Animals, Genetically Modified/metabolism , Neurodegenerative Diseases/metabolism , Neurons/metabolism , Parkinson Disease/metabolism , Animals , Animals, Genetically Modified/genetics , Caenorhabditis elegans/metabolism , Disease Models, Animal , Humans
9.
Drug Discov Ther ; 14(6): 262-272, 2021 Jan 23.
Article in English | MEDLINE | ID: covidwho-1067907

ABSTRACT

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in 2019 in Wuhan, China. Clinically, respiratory tract symptoms as well as other organs disorders are observed in patients positively diagnosed coronavirus disease 2019 (COVID-19). In addition, neurological symptoms, mainly anosmia, ageusia and headache were observed in many patients. Once in the central nervous system (CNS), the SARS-CoV-2 can reside either in a quiescent latent state, or eventually in actively state leading to severe acute encephalitis, characterized by neuroinflammation and prolonged neuroimmune activation. SRAS-CoV-2 requires angiotensin-converting enzyme 2 (ACE2) as a cell entry receptor. The expression of this receptor in endothelial cells of blood-brain barrier (BBB) shows that SRAS-CoV-2 may have higher neuroinvasive potential compared to known coronaviruses. This review summarizes available information regarding the impact of SRAS-CoV-2 in the brain and tended to identify its potential pathways of neuroinvasion. We offer also an understanding of the long-term impact of latently form of SARS-CoV-2 on the development of neurodegenerative disorders. As a conclusion, the persistent infection of SRAS-CoV-2 in the brain could be involved on human neurodegenerative diseases that evolve a gradual process, perhapes, over several decades.


Subject(s)
COVID-19/virology , Central Nervous System Viral Diseases/virology , Neurodegenerative Diseases/virology , Neurons/virology , SARS-CoV-2/pathogenicity , Viral Tropism , Animals , COVID-19/complications , Central Nervous System Viral Diseases/metabolism , Central Nervous System Viral Diseases/pathology , Host-Pathogen Interactions , Humans , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Neurons/metabolism , Neurons/pathology , Virus Latency
10.
Brain Behav Immun ; 91: 740-755, 2021 01.
Article in English | MEDLINE | ID: covidwho-1064860

ABSTRACT

Central nervous system (CNS) innate immunity plays essential roles in infections, neurodegenerative diseases, and brain or spinal cord injuries. Astrocytes and microglia are the principal cells that mediate innate immunity in the CNS. Pattern recognition receptors (PRRs), expressed by astrocytes and microglia, sense pathogen-derived or endogenous ligands released by damaged cells and initiate the innate immune response. Toll-like receptors (TLRs) are a well-characterized family of PRRs. The contribution of microglial TLR signaling to CNS pathology has been extensively investigated. Even though astrocytes assume a wide variety of key functions, information about the role of astroglial TLRs in CNS disease and injuries is limited. Because astrocytes display heterogeneity and exhibit phenotypic plasticity depending on the effectors present in the local milieu, they can exert both detrimental and beneficial effects. TLRs are modulators of these paradoxical astroglial properties. The goal of the current review is to highlight the essential roles played by astroglial TLRs in CNS infections, injuries and diseases. We discuss the contribution of astroglial TLRs to host defense as well as the dissemination of viral and bacterial infections in the CNS. We examine the link between astroglial TLRs and the pathogenesis of neurodegenerative diseases and present evidence showing the pivotal influence of astroglial TLR signaling on sterile inflammation in CNS injury. Finally, we define the research questions and areas that warrant further investigations in the context of astrocytes, TLRs, and CNS dysfunction.


Subject(s)
Astrocytes/metabolism , Neurodegenerative Diseases/physiopathology , Toll-Like Receptors/physiology , Animals , Astrocytes/physiology , Brain/metabolism , Central Nervous System/immunology , Central Nervous System/metabolism , Central Nervous System Diseases/immunology , Central Nervous System Infections/pathology , Encephalitis/immunology , Humans , Immunity, Innate/physiology , Microglia/metabolism , Neurodegenerative Diseases/metabolism , Neurons/metabolism , Receptors, Pattern Recognition/immunology , Signal Transduction , Spinal Cord/pathology , Spinal Cord Injuries/pathology , Toll-Like Receptors/metabolism
11.
Trends Neurosci ; 44(2): 83-96, 2021 02.
Article in English | MEDLINE | ID: covidwho-916894

ABSTRACT

Recognition of foreign or misplaced nucleic acids is one of the principal modes by which the immune system detects pathogenic entities. When cytosolic DNA is sensed, a signal is relayed via the cGAS-STING pathway: this involves the activation of cyclic GMP-AMP (cGMP-AMP) synthase (cGAS) and generation of the cyclic dinucleotide cGAMP, followed by the induction of stimulator of interferon genes (STING). The cGAS-STING pathway responds to viral, bacterial, and self-DNA. Whereas it generally mediates immune surveillance and is often neuroprotective, excessive engagement of the system can be deleterious. This is relevant in aging and age-related neurological diseases, where neuroinflammation contributes to disease progression. This review focuses on cGAS-STING signaling in aging, neurodegeneration, and neuroinflammation, and on therapeutic implications.


Subject(s)
Membrane Proteins , Neurodegenerative Diseases/metabolism , Nucleotidyltransferases , Aging , DNA , Humans , Membrane Proteins/metabolism , Nucleotidyltransferases/metabolism , Signal Transduction
12.
Cells ; 10(1)2020 12 24.
Article in English | MEDLINE | ID: covidwho-1000241

ABSTRACT

Protein homeostasis is maintained by removing misfolded, damaged, or excess proteins and damaged organelles from the cell by three major pathways; the ubiquitin-proteasome system, the autophagy-lysosomal pathway, and the endo-lysosomal pathway. The requirement for ubiquitin provides a link between all three pathways. Sorting nexins are a highly conserved and diverse family of membrane-associated proteins that not only traffic proteins throughout the cells but also provide a second common thread between protein homeostasis pathways. In this review, we will discuss the connections between sorting nexins, ubiquitin, and the interconnected roles they play in maintaining protein quality control mechanisms. Underlying their importance, genetic defects in sorting nexins are linked with a variety of human diseases including neurodegenerative, cardiovascular diseases, viral infections, and cancer. This serves to emphasize the critical roles sorting nexins play in many aspects of cellular function.


Subject(s)
Endosomes/metabolism , Lysosomes/metabolism , Proteasome Endopeptidase Complex/metabolism , Proteostasis , Sorting Nexins , Ubiquitin/metabolism , Autophagy , Cardiovascular Diseases/metabolism , Humans , Neoplasms/metabolism , Neurodegenerative Diseases/metabolism , Sorting Nexins/genetics , Sorting Nexins/physiology , Virus Diseases/metabolism , Yeasts
13.
Aging (Albany NY) ; 12(23): 24453-24461, 2020 11 10.
Article in English | MEDLINE | ID: covidwho-927217

ABSTRACT

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) uses the angiotensin-converting enzyme 2 (ACE2) receptor for infecting and spreading in humans. Studies have shown that the widespread expression of ACE2 in human tissues may be associated with organ function damage (e.g., lung, kidney, and stomach) in patients with coronavirus disease 2019 (COVID-19). However, in neurodegenerative diseases, whose pathogenesis is closely related to advanced age, ACE2 plays a neurotrophic and protective role by activating the ACE2/Ang-(1-7)/Mas axis, thus inhibiting cognitive impairment. Early reports have revealed that the elderly are more susceptible to COVID-19 and that elderly patients with COVID-19 have faster disease progression and higher mortality. Therefore, during the COVID-19 pandemic, it is crucial to understand the role of ACE2 in neurodegenerative diseases. In this paper, we review the relationship between COVID-19, neurodegenerative diseases, and ACE2, as well as provide recommendations for the protection of elderly patients with neurodegenerative diseases during the COVID-19 pandemic.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/complications , COVID-19/virology , Neurodegenerative Diseases/etiology , Neurodegenerative Diseases/metabolism , SARS-CoV-2 , Age Factors , Angiotensin-Converting Enzyme 2/genetics , Disease Susceptibility , Host-Pathogen Interactions , Humans , Neurodegenerative Diseases/pathology , Renin-Angiotensin System , Risk Factors , SARS-CoV-2/physiology
15.
Biomolecules ; 10(8)2020 08 07.
Article in English | MEDLINE | ID: covidwho-823584

ABSTRACT

Neurodegenerative diseases are the second most common cause of death and characterized by progressive impairments in movement or mental functioning in the central or peripheral nervous system. The prevention of neurodegenerative disorders has become an emerging public health challenge for our society. Melatonin, a pineal hormone, has various physiological functions in the brain, including regulating circadian rhythms, clearing free radicals, inhibiting biomolecular oxidation, and suppressing neuroinflammation. Cumulative evidence indicates that melatonin has a wide range of neuroprotective roles by regulating pathophysiological mechanisms and signaling pathways. Moreover, melatonin levels are decreased in patients with neurodegenerative diseases. In this review, we summarize current knowledge on the regulation, molecular mechanisms and biological functions of melatonin in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, vascular dementia and multiple sclerosis. We also discuss the clinical application of melatonin in neurodegenerative disorders. This information will lead to a better understanding of the regulation of melatonin in the brain and provide therapeutic options for the treatment of various neurodegenerative diseases.


Subject(s)
Circadian Rhythm , Melatonin/physiology , Neurodegenerative Diseases/metabolism , Oxidative Stress , Alzheimer Disease/metabolism , Amyotrophic Lateral Sclerosis/metabolism , Animals , Circadian Rhythm/drug effects , Dementia, Vascular/metabolism , Humans , Huntington Disease/metabolism , Melatonin/therapeutic use , Multiple Sclerosis/metabolism , Neurodegenerative Diseases/drug therapy , Oxidative Stress/drug effects , Parkinson Disease/metabolism
16.
Cells ; 9(9)2020 08 26.
Article in English | MEDLINE | ID: covidwho-730307

ABSTRACT

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role in cell-cell communications. Exosomes have evolved as potential biomarkers for aging-related diseases. Aging, a physiological process, involves a progressive decline of function of organs with a loss of homeostasis and increasing probability of illness and death. The review focuses on the classic view of exosome biogenesis, biology, and age-associated changes. Owing to their ability to transport biological information among cells, the review also discusses the interplay of senescent cell-derived exosomes with the aging process, including the susceptibility of the aging population to COVID-19 infections.


Subject(s)
Aging/metabolism , Cardiovascular Diseases/metabolism , Cell Communication , Cellular Senescence , Coronavirus Infections/metabolism , Diabetes Mellitus/metabolism , Exosomes/metabolism , Extracellular Vesicles/metabolism , Neurodegenerative Diseases/metabolism , Pneumonia, Viral/metabolism , Aged , Aged, 80 and over , Animals , Betacoronavirus , Biomarkers/metabolism , COVID-19 , Coronavirus Infections/virology , Humans , Mice , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2
17.
ACS Chem Neurosci ; 11(13): 1887-1899, 2020 07 01.
Article in English | MEDLINE | ID: covidwho-505648

ABSTRACT

The coronavirus disease-19 (COVID-19) pandemic has emerged as one of the major outbreaks to be mentioned in history in coming times. Like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a respiratory virus infecting the lungs with fever, dry cough, and acute pneumonia being the major symptoms. It infects epithelial cells expressing angiotensin converting enzyme 2 (ACE2) receptor, which is crucial for viral entry. Based on evolving clinical evidence, it is now unfitting to label SARS-CoV-2 as just a respiratory virus, as lately there are various reports that substantiate its pathogenicity in other organs of the body, including brain. In this review, we discuss the epidemiology of SARS-CoV-2 in comparison to SARS and MERS along with possibilities of viral entry into central nervous system (CNS) tissues. The review provides detailed information about the virulence, epidemiology, and insights into molecular pathways involved in the infectivity of the SARS-CoV-2 virus, along with an in-depth view of current concepts about the neurological significance of the SARS-CoV-2 virus and its neuropathological competence. The review also touches upon our current understanding of placental transmission of SARS-CoV-2, an important aspect of vertical transmission. Furthermore, the review provides a current update on strategies that have been used, are being used, or are under trial for treating the disease.


Subject(s)
Betacoronavirus/metabolism , Brain/metabolism , Coronavirus Infections/metabolism , Neurodegenerative Diseases/metabolism , Pneumonia, Viral/metabolism , Angiotensin-Converting Enzyme 2 , Brain/pathology , Brain/virology , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Humans , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/virology , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/metabolism , Severe Acute Respiratory Syndrome/pathology
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