Covid-19, nervous system pathology, and Parkinson's disease: Bench to bedside

Emmi, Aron; Boura, Iro; Raeder, Vanessa; Mathew, Donna; Sulzer, David; Goldman, James E.; Leta, Valentina

doi:10.1016/bs.irn.2022.06.006

Cited by 9 publications

(7 citation statements)

References 92 publications

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“…Furthermore, the authors demonstrated that αSyn upregulation and aggregation was accelerated by SARS-CoV-2 viral proteins, and that overexpression of αSyn led to the development of Lewy-body pathology in vitro. Hence, while αSyn expression increases in neurons in response to infection, the presence of viral proteins can potentially trigger protein misfolding and aggregation as seen in in vitro studies, especially in conjunction with inflammatory, environmental and genetic facilitators, leading toward, or predisposing to, synucleinopathies and neurodegeneration 37 , 38 .…”

Section: Discussionmentioning

confidence: 99%

Detection of SARS-CoV-2 viral proteins and genomic sequences in human brainstem nuclei

Emmi

Rizzo

Barzon

et al. 2023

npj Parkinsons Dis.

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Neurological manifestations are common in COVID-19, the disease caused by SARS-CoV-2. Despite reports of SARS-CoV-2 detection in the brain and cerebrospinal fluid of COVID-19 patients, it is still unclear whether the virus can infect the central nervous system, and which neuropathological alterations can be ascribed to viral tropism, rather than immune-mediated mechanisms. Here, we assess neuropathological alterations in 24 COVID-19 patients and 18 matched controls who died due to pneumonia/respiratory failure. Aside from a wide spectrum of neuropathological alterations, SARS-CoV-2-immunoreactive neurons were detected in the dorsal medulla and in the substantia nigra of five COVID-19 subjects. Viral RNA was also detected by real-time RT-PCR. Quantification of reactive microglia revealed an anatomically segregated pattern of inflammation within affected brainstem regions, and was higher when compared to controls. While the results of this study support the neuroinvasive potential of SARS-CoV-2 and characterize the role of brainstem inflammation in COVID-19, its potential implications for neurodegeneration, especially in Parkinson’s disease, require further investigations.

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Section: Discussionmentioning

confidence: 99%

Detection of SARS-CoV-2 viral proteins and genomic sequences in human brainstem nuclei

Emmi

Rizzo

Barzon

et al. 2023

npj Parkinsons Dis.

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“…The constellation of neurological symptoms reported following SARS-CoV-2 infection include headache, dizziness, delirium, encephalopathy, ataxia, seizures, increased stroke risk, and encephalitis and also suggest peripheral nervous system involvement (vision and smell impairments, sympathoactivation, etc. ). − Neuropathological findings in COVID-19 patients include hypoxic–ischemic damage, neuroinflammation with prominent microgliosis and lympho-monocytic infiltrates, as well as instances suggesting SARS-CoV-2 neurotropism. We have previously demonstrated that SARS-CoV-2 viral proteins and genomic sequences can be detected in specific brainstem nuclei of a subset of COVID-19 decedents and that microglial cells present a topographically defined pattern of distribution within the brainstem while also displaying a more severe inflammatory phenotype compared to pneumonia subjects .…”

Section: Introductionmentioning

confidence: 99%

ACE2 Receptor and TMPRSS2 Protein Expression Patterns in the Human Brainstem Reveal Anatomical Regions Potentially Vulnerable to SARS-CoV-2 Infection

Emmi,

Tushevski,

Sinigaglia

et al. 2023

ACS Chem. Neurosci.

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Angiotensin-converting enzyme 2 receptor (ACE2R) is a transmembrane protein expressed in various tissues throughout the body that plays a key role in the regulation of blood pressure. Recently, ACE2R has gained significant attention due to its involvement in the pathogenesis of COVID-19, the disease caused by the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). While ACE2 receptors serve as entry points for the novel coronavirus, Transmembrane Serine Protease 2 (TMPRSS2), an enzyme located on the cell membrane, is required for SARS-CoV-2 S protein priming. Even though numerous studies have assessed the effects of COVID-19 on the brain, very little information is available concerning the distribution of ACE2R and TMPRSS2 in the human brain, with particular regard to their topographical expression in the brainstem. In this study, we investigated the expression of ACE2R and TMPRSS2 in the brainstem of 18 adult subjects who died due to pneumonia/respiratory insufficiency. Our findings indicate that ACE2R and TMPRSS2 are expressed in neuronal and glial cells of the brainstem, particularly at the level of the vagal nuclei of the medulla and the midbrain tegmentum, thus confirming the expression and anatomical localization of these proteins within specific human brainstem nuclei. Furthermore, our findings help to define anatomically susceptible regions to SARS-CoV-2 infection in the brainstem, advancing knowledge on the neuropathological underpinnings of neurological manifestations in COVID-19.

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“…In addition to the effects of old age, comorbidities, and genetics described above, immune and inflammatory responses appear to play an important role in promoting AD death. However, there is little evidence to support SARS-CoV-2 infection of central nervous system cells, and most neurological symptoms appear to be due to hypoxia/ischemia and/or damage mediated by inflammatory damage ( 76 ). For example, Mao L et al found that COVID-19 can induce uncontrolled cytokine storms (mainly involving IL-6, IL-1β, and TNF), leading to a variety of symptoms including delirium ( 55 ).…”

Section: Why Individuals With Alzheimer’s Disease Are Most Likely To ...mentioning

confidence: 99%

Alzheimer’s disease and COVID-19: Interactions, intrinsic linkages, and the role of immunoinflammatory responses in this process

Sun

Yue

et al. 2023

Front. Immunol.

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Alzheimer’s disease (AD) and COVID-19 share many common risk factors, such as advanced age, complications, APOE genotype, etc. Epidemiological studies have also confirmed the internal relationship between the two diseases. For example, studies have found that AD patients are more likely to suffer from COVID-19, and after infection with COVID-19, AD also has a much higher risk of death than other chronic diseases, and what’s more interesting is that the risk of developing AD in the future is significantly higher after infection with COVID-19. Therefore, this review gives a detailed introduction to the internal relationship between Alzheimer’s disease and COVID-19 from the perspectives of epidemiology, susceptibility and mortality. At the same time, we focused on the important role of inflammation and immune responses in promoting the onset and death of AD from COVID-19.

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Covid-19, nervous system pathology, and Parkinson's disease: Bench to bedside

Cited by 9 publications

References 92 publications

Detection of SARS-CoV-2 viral proteins and genomic sequences in human brainstem nuclei

Detection of SARS-CoV-2 viral proteins and genomic sequences in human brainstem nuclei

ACE2 Receptor and TMPRSS2 Protein Expression Patterns in the Human Brainstem Reveal Anatomical Regions Potentially Vulnerable to SARS-CoV-2 Infection

Alzheimer’s disease and COVID-19: Interactions, intrinsic linkages, and the role of immunoinflammatory responses in this process

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