Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
Am J Alzheimers Dis Other Demen ; 37: 15333175221078418, 2022.
Article in English | MEDLINE | ID: covidwho-1673841

ABSTRACT

A significant portion of COVID-19 patients and survivors display marked clinical signs of neurocognitive impairments. SARS-CoV-2-mediated peripheral cytokine storm and its neurotropism appear to elicit the activation of glial cells in the brain proceeding to neuroinflammation. While adult neurogenesis has been identified as a key cellular basis of cognitive functions, neuroinflammation-induced aberrant neuroregenerative plasticity in the hippocampus has been implicated in progressive memory loss in ageing and brain disorders. Notably, recent histological studies of post-mortem human and experimental animal brains indicate that SARS-CoV-2 infection impairs neurogenic process in the hippocampus of the brain due to neuroinflammation. Considering the facts, this article describes the prominent neuropathogenic characteristics and neurocognitive impairments in COVID-19 and emphasizes a viewpoint that neuroinflammation-mediated deterioration of hippocampal neurogenesis could contribute to the onset and progression of dementia in COVID-19. Thus, it necessitates the unmet need for regenerative medicine for the effective management of neurocognitive deficits in COVID-19.


Subject(s)
COVID-19 , Dementia , Animals , Hippocampus , Humans , Neurogenesis , SARS-CoV-2
2.
Naunyn Schmiedebergs Arch Pharmacol ; 394(3): 561-567, 2021 03.
Article in English | MEDLINE | ID: covidwho-1235720

ABSTRACT

Coronavirus disease 2019 (COVID-19) has been characterized by lymphopenia as well as a proinflammatory cytokine storm, which are responsible for the poor prognosis and multiorgan defects. The transcription factor nuclear factor-κB (NF-κB) modulates the functions of the immune cells and alters the gene expression profile of different cytokines in response to various pathogenic stimuli, while many proinflammatory factors have been known to induce NF-κB signalling cascade. Besides, NF-κB has been known to potentiate the production of reactive oxygen species (ROS) leading to apoptosis in various tissues in many diseases and viral infections. Though the reports on the involvement of the NF-κB signalling pathway in COVID-19 are limited, the therapeutic benefits of NF-κB inhibitors including dexamethasone, a synthetic form of glucocorticoid, have increasingly been realized. Considering the fact, the abnormal activation of the NF-κB resulting from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection might be associated with the pathogenic profile of immune cells, cytokine storm and multiorgan defects. Thus, the pharmacological inactivation of the NF-κB signalling pathway can strongly represent a potential therapeutic target to treat the symptomatology of COVID-19. This article signifies pharmacological blockade of the phosphorylation of inhibitor of nuclear factor kappa B kinase subunit beta (IKKß), a key downstream effector of NF-κB signalling, for a therapeutic consideration to attenuate COVID-19.


Subject(s)
COVID-19/drug therapy , Drug Delivery Systems/trends , I-kappa B Kinase/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Signal Transduction/physiology , Animals , COVID-19/epidemiology , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/metabolism , Heterocyclic Compounds, 3-Ring/administration & dosage , Humans , I-kappa B Kinase/metabolism , Lymphopenia/drug therapy , Lymphopenia/epidemiology , Lymphopenia/metabolism , NF-kappa B/metabolism , Nitriles/administration & dosage , Pyridines/administration & dosage , Signal Transduction/drug effects , Sulfones/administration & dosage
3.
J Chem Neuroanat ; 115: 101965, 2021 09.
Article in English | MEDLINE | ID: covidwho-1225275

ABSTRACT

Anosmia, a neuropathogenic condition of loss of smell, has been recognized as a key pathogenic hallmark of the current pandemic SARS-CoV-2 infection responsible for COVID-19. While the anosmia resulting from olfactory bulb (OB) pathology is the prominent clinical characteristic of Parkinson's disease (PD), SARS-CoV-2 infection has been predicted as a potential risk factor for developing Parkinsonism-related symptoms in a significant portion of COVID-19 patients and survivors. SARS-CoV-2 infection appears to alter the dopamine system and induce the loss of dopaminergic neurons that have been known to be the cause of PD. However, the underlying biological basis of anosmia and the potential link between COVID-19 and PD remains obscure. Ample experimental studies in rodents suggest that the occurrence of neural stem cell (NSC) mediated neurogenesis in the olfactory epithelium (OE) and OB is important for olfaction. Though the occurrence of neurogenesis in the human forebrain has been a subject of debate, considerable experimental evidence strongly supports the incidence of neurogenesis in the human OB in adulthood. To note, various viral infections and neuropathogenic conditions including PD with olfactory dysfunctions have been characterized by impaired neurogenesis in OB and OE. Therefore, this article describes and examines the recent reports on SARS-CoV-2 mediated OB dysfunctions and defects in the dopaminergic system responsible for PD. Further, the article emphasizes that COVID-19 and PD associated anosmia could result from the regenerative failure in the replenishment of the dopaminergic neurons in OB and olfactory sensory neurons in OE.


Subject(s)
Anosmia/etiology , Anosmia/pathology , COVID-19/complications , COVID-19/pathology , Neurogenesis , Olfaction Disorders/etiology , Olfaction Disorders/pathology , Parkinson Disease/complications , Parkinson Disease/pathology , Animals , Humans
4.
Reprod Sci ; 28(10): 2735-2742, 2021 10.
Article in English | MEDLINE | ID: covidwho-1014275

ABSTRACT

Coronavirus disease 2019 (COVID-19), which resulted from the pandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a massive inflammatory cytokine storm leading to multi-organ damage including that of the brain and testes. While the lungs, heart, and brain are identified as the main targets of SARS-CoV-2-mediated pathogenesis, reports on its testicular infections have been a subject of debate. The brain and testes are physiologically synchronized by the action of gonadotropins and sex steroid hormones. Though the evidence for the presence of the viral particles in the testicular biopsies and semen samples from COVID-19 patients are highly limited, the occurrence of testicular pathology due to abrupt inflammatory responses and hyperthermia has incresingly been evident. The reduced level of testosterone production in COVID-19 is associated with altered secretion of gonadotropins. Moreover, hypothalamic pathology which results from SARS-CoV-2 infection of the brain is also evident in COVID-19 cases. This article revisits and supports the key reports on testicular abnormalities and pathological signatures in the hypothalamus of COVID-19 patients and emphasizes that testicular pathology resulting from inflammation and oxidative stress might lead to infertility in a significant portion of COVID-19 survivors. Further investigations are required to monitor the reproductive health parameters and HPG axis abnormalities related to secondary pathological complications in COVID-19 patients and survivors.


Subject(s)
COVID-19/epidemiology , Fertility , Hypothalamus/pathology , Infertility, Male/epidemiology , SARS-CoV-2/pathogenicity , Testis/pathology , Animals , Atrophy , COVID-19/diagnosis , COVID-19/virology , Gonadotropins/metabolism , Host-Pathogen Interactions , Humans , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/pathology , Hypothalamo-Hypophyseal System/physiopathology , Hypothalamo-Hypophyseal System/virology , Hypothalamus/metabolism , Hypothalamus/physiopathology , Hypothalamus/virology , Incidence , Infertility, Male/pathology , Infertility, Male/physiopathology , Infertility, Male/virology , Male , Testis/metabolism , Testis/physiopathology , Testis/virology , Testosterone/metabolism
5.
Life Sci ; 266: 118883, 2021 Feb 01.
Article in English | MEDLINE | ID: covidwho-974347

ABSTRACT

Coronavirus disease 2019 (COVID-19) has rapidly spread around the world causing global public health emergency. In the last twenty years, we have witnessed several viral epidemics such as severe acute respiratory syndrome coronavirus (SARS-CoV), Influenza A virus subtype H1N1 and most recently Middle East respiratory syndrome coronavirus (MERS-CoV). There were tremendous efforts endeavoured globally by scientists to combat these viral diseases and now for SARS-CoV-2. Several drugs such as chloroquine, arbidol, remdesivir, favipiravir and dexamethasone are adopted for use against COVID-19 and currently clinical studies are underway to test their safety and efficacy for treating COVID-19 patients. As per World Health Organization reports, so far more than 16 million people are affected by COVID-19 with a recovery of close to 10 million and deaths at 600,000 globally. SARS-CoV-2 infection is reported to cause extensive pulmonary damages in affected people. Given the large number of recoveries, it is important to follow-up the recovered patients for apparent lung function abnormalities. In this review, we discuss our understanding about the development of long-term pulmonary abnormalities such as lung fibrosis observed in patients recovered from coronavirus infections (SARS-CoV and MERS-CoV) and probable epigenetic therapeutic strategy to prevent the development of similar pulmonary abnormalities in SARS-CoV-2 recovered patients. In this regard, we address the use of U.S. Food and Drug Administration (FDA) approved histone deacetylase (HDAC) inhibitors therapy to manage pulmonary fibrosis and their underlying molecular mechanisms in managing the pathologic processes in COVID-19 recovered patients.


Subject(s)
COVID-19/complications , Drug Repositioning , Histone Deacetylase Inhibitors/therapeutic use , Pulmonary Fibrosis/drug therapy , Transforming Growth Factor beta/metabolism , Adult , Aged , COVID-19/pathology , COVID-19/therapy , Coronavirus Infections/pathology , Extracellular Matrix/pathology , Extracellular Matrix/virology , Histone Deacetylase Inhibitors/pharmacology , Humans , Middle Aged , Pulmonary Fibrosis/virology , Risk Factors , Signal Transduction , Survivors
6.
Med Drug Discov ; 6: 100042, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-141614

ABSTRACT

The recent outbreak of coronavirus disease (COVID-19) resulting from a distinctive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to evolve in many countries and pose life-threatening clinical issues to global public health. While the lungs are the primary target for the SARS-CoV-2-mediated pathological consequence, the virus appears to invade the brain and cause unpredicted neurological deficits. In the later stage, COVID-19 can progress to pneumonia, acute respiratory failure, neurodegeneration and multi-organ dysfunctions leading to death. Though a significant portion of individuals with COVID-19 has been recovering from clinical symptoms, the pathological impact of the SARS-CoV-2 infection on the structural and functional properties of the lungs, heart, brain and other organs at the post-recovery state remains unknown. Presently, there is an urgent need for a remedial measure to combat this devastating COVID-19. Botulinum toxins (BoNTs) are potent neurotoxins that can induce paralysis of muscle and acute respiratory arrest in humans. However, a mild dose of the purified form of BoNT has been known to attenuate chronic cough, dyspnoea, pneumonia, acute respiratory failure, abnormal circulation, cardiac defects and various neurological deficits that have been recognised as the prominent clinical symptoms of COVID-19. Considering the fact, this review article provides 1) an overview of the SARS-CoV-2 mediated pathological impact on the lungs, heart and brain, 2) signifies the therapeutic uses of BoNTs against pulmonary failure, cardiac arrest and neurological deficits, and 3) emphasize the rationality for the possible use of BoNT to prevent SARS-CoV-2 infection and manage COVID-19.

SELECTION OF CITATIONS
SEARCH DETAIL