The Potential Role of SARS-COV-2 in the Pathogenesis of Parkinson's Disease

Abstract

Considering their current burden and epidemiological projections, nowadays Parkinson's disease and the COVID-19 pandemic are two key health problems. There is evidence of the pathogenic role of neurotropic viruses in neurodegenerative diseases and coronaviruses are neurotropic, with some of them selectively targeting the basal ganglia. Moreover, some authors demonstrated the longevity of these viruses in the affected cells of the nervous system for long periods. Coronavirus was detected in brain autopsies and SARS-CoV-2 has been isolated from the CSF of affected patients. The marked inflammatory response in some particular patients with COVID-19 with a consequent increase of pro-inflammatory cytokines is considered a prognostic factor. Immunologic changes are observed in patients with Parkinson's disease, possibly having a role in its pathogenesis. A dynamic pro-inflammatory state accompanies α-synuclein accumulation and the development and progression of neurodegeneration. Also, some viral infectious diseases might have a role as triggers, generating a cross autoimmune reaction against α-synuclein. In the past Coronaviruses have been related to Parkinson's disease, however, until now the causal role of these viruses is unknown. In this paper, our focus is to assess the potential relationship between SARS-CoV-2 infection and Parkinson's disease.

Keywords: Parkinson disease; SARS virus; alpha-synuclein; coronavirus; movement disorders; nervous system diseases; neurodegenerative diseases; pandemics.

Figure 1

Triggering factors of the neuroinflammatory process. Aging, in addition to genetic and environmental factors, and infections of certain microorganisms, can trigger a neuroinflammatory response through microglial and oligodendroglial activation. Activated microglia adopt an M1 inflammatory phenotype, secreting proinflammatory cytokines, reactive oxygen species (ROS), and glutamate; factors that cause neuronal damage. In this context, astrocytes become reactive, and like microglia, they secrete proinflammatory cytokines. Many of these cytokines act on microglial cells, exacerbating microglial activation, and favoring neuronal damage. The release of TNF-alpha by microglia induces increased glutamate release by astrocytes: a detrimental event for neurons. In this context, degenerating and/or dead neurons are observed, which in turn trigger microglial activation. Protein accumulation (e.g., alpha-synuclein) is another triggering factor for microglial activation. Microglia degrades and presents components of dead cells and protein aggregates to CD4+ T lymphocytes. This, in conjunction with the release of cytokines, results in the infiltration of CD4 + T cells, which release more proinflammatory cytokines, leading to greater neurodegeneration. As a consequence of this neuroinflammation, the blood-brain barrier (BBB) becomes dysfunctional, leading to the entry of peripheral immune cells. In the periphery, gut microbiota can trigger inflammation mediated by innate immune cells. The SARS-CoV-2 virus generates a “cytokine storm” at the peripheral level, therefore, it could have a similar effect. Inflammatory cytokines from peripheral blood circulation could also contribute to BBB permeabilization.