The Intersection of Parkinson’s Disease, Viral Infections, and COVID-19

Abstract

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of human COVID-19, not only causes flu-like symptoms and gut microbiome complications but a large number of infected individuals also experience a host of neurological symptoms including loss of smell and taste, seizures, difficulty concentrating, decreased alertness, and brain inflammation. Although SARS-CoV-2 infections are not more prevalent in Parkinson's disease patients, a higher mortality rate has been reported not only associated with older age and longer disease duration, but also through several mechanisms, such as interactions with the brain dopaminergic system and through systemic inflammatory responses. Indeed, a number of the neurological symptoms seen in COVID-19 patients, as well as the alterations in the gut microbiome, are also prevalent in patients with Parkinson's disease. Furthermore, biochemical pathways such as oxidative stress, inflammation, and protein aggregation have shared commonalities between Parkinson's disease and COVID-19 disease progression. In this review, we describe and compare the numerous similarities and intersections between neurodegeneration in Parkinson's disease and RNA viral infections, emphasizing the current SARS-CoV-2 global health crisis.

SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro

“…There is also mounting evidence supporting the association of inflammation, mitochondrial dysfunction, autophagy deficiency, endoplasmic reticulum stress, and loss of proteostasis by SARS-CoV-2 infection with an elevated risk of PD later in life [ 4 ]. Several biochemical pathways, including oxidative stress, inflammation, and protein aggregation, show similarities between PD and COVID-19 [ 2 ].…”

“…The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks known as the 2019 novel coronavirus disease (COVID-19) pandemic has caused high levels of concern and economic crisis around the world [ 1 ]. Previous studies have supported a link between SARS-CoV-2 infection and Parkinson’s diseases (PD) [ 2 , 3 , 4 , 5 ]. More recently, several cases of patients with COVID-19 who developed parkinsonism and responded to levodopa have been reported.…”

TLR2 and TLR4 in Parkinson’s disease pathogenesis: the environment takes a toll on the gut

“…For example, infection with West Nile virus increases α-synuclein protein levels in primary striatal neurons in vitro, while α-synuclein-knockout mice exhibit higher viral load and mortality after infection with West Nile virus and Venezuelan equine encephalitis virus in comparison to wild-type and heterozygous littermates, supporting a role of α-synuclein in the inhibition of viral replication and associated viral pathology [ 161 ]. Of particular note, growing numbers of acute parkinsonism following Severe Acute Respiratory Syndrome Coronavirus 2 infection are being reported [ 173 , 174 ], and coronavirus disease 2019 (COVID-19) affects both the olfactory (anosmia) and the gastrointestinal tracts (microbial dysbiosis, diarrhoea and colonic inflammation) in some people, reflecting Braak’s two hypothesised PD initiation sites [ 175 ]. Furthermore, a number of molecular similarities have been identified between COVID-19 and PD, including oxidative stress, inflammation and protein aggregation [ 175 ].…”

“…Of particular note, growing numbers of acute parkinsonism following Severe Acute Respiratory Syndrome Coronavirus 2 infection are being reported [ 173 , 174 ], and coronavirus disease 2019 (COVID-19) affects both the olfactory (anosmia) and the gastrointestinal tracts (microbial dysbiosis, diarrhoea and colonic inflammation) in some people, reflecting Braak’s two hypothesised PD initiation sites [ 175 ]. Furthermore, a number of molecular similarities have been identified between COVID-19 and PD, including oxidative stress, inflammation and protein aggregation [ 175 ]. Although there is currently insufficient longitudinal data to link COVID-19 infection or “long COVID” with a risk of developing PD, future research on the associations between viral infections, TLR signalling, α-synuclein and PD is critical in light of the ongoing pandemic.…”

Can SARS-CoV-2 Infection Lead to Neurodegeneration and Parkinson’s Disease?

“…On the other hand, a protective role of α-synuclein against COVID-19 was proposed since α-synuclein, like β-amyloid, is upregulated in the face of viral infections and can restrict viral replication acting as a defense mechanism in the brain [ 108 ]. This leads to the speculation that PD patients with higher α-synuclein levels in the brain might have some protection against SARS-CoV-2 infection [ 109 ].…”