Role of SARS-CoV-2 in Modifying Neurodegenerative Processes in Parkinson’s Disease: A Narrative Review

Abstract

The COVID-19 pandemic, caused by SARS-CoV-2, continues to impact global health regarding both morbidity and mortality. Although SARS-CoV-2 primarily causes acute respiratory distress syndrome (ARDS), the virus interacts with and influences other organs and tissues, including blood vessel endothelium, heart, gastrointestinal tract, and brain. We are learning much about the pathophysiology of SARS-CoV-2 infection; however, we are just beginning to study and understand the long-term and chronic health consequences. Since the pandemic’s beginning in late 2019, older adults, those with pre-existing illnesses, or both, have an increased risk of contracting COVID-19 and developing severe COVID-19. Furthermore, older adults are also more likely to develop the neurodegenerative disorder Parkinson’s disease (PD), with advanced age as the most significant risk factor. Thus, does SARS-CoV-2 potentially influence, promote, or accelerate the development of PD in older adults? Our initial focus was aimed at understanding SARS-CoV-2 pathophysiology and the connection to neurodegenerative disorders. We then completed a literature review to assess the relationship between PD and COVID-19. We described potential molecular and cellular pathways that indicate dopaminergic neurons are susceptible, both directly and indirectly, to SARS-CoV-2 infection. We concluded that under certain pathological circumstances, in vulnerable persons-with-Parkinson’s disease (PwP), SARS-CoV-2 acts as a neurodegenerative enhancer to potentially support the development or progression of PD and its related motor and non-motor symptoms.

Post-COVID-19 Parkinsonism and Parkinson’s Disease Pathogenesis: The Exosomal Cargo Hypothesis

“…SARS-CoV-2 seems to interact with and manipulate mitochondria in order to hijack and evade mitochondria-mediated immune response for its own replication and survival [ 179 , 180 ]. In this effort, SARS-CoV-2 may induce mitochondrial impairment [ 181 , 182 ], mitochondria-mediated oxidative stress, and mitochondrial damage through mitochondrial membrane depolarization, mitochondrial permeability transition pore opening, and enhanced ROS release [ 183 , 184 , 185 ]. Furthermore, the virus prevents mitophagy by blocking the binding of p62 and microtubule-associated protein 1A/1B-light chain 3 (LC3), thereby hindering viral RNA breakdown [ 185 ].…”

Links between COVID-19 and Parkinson’s disease/Alzheimer’s disease: reciprocal impacts, medical care strategies and underlying mechanisms

“…It has been reported that SARS-CoV-2 is able to enter the brain and trigger the release of inflammatory mediators [ 34 ] that are known to play a role in neurodegeneration. SARS-CoV-2 can enter the brain by invading the olfactory bulb, by axonal transport from peripheral nerves, and by hematogenous pathways through the BBB [ 35 ]. SARS-CoV-2 could bind to ACE2 receptors on dopaminergic neurons, altering the rate of accumulation of misfolded α-synuclein, and promoting mitochondria stress, autophagy, and apoptosis [ 35 , 36 ].…”

“…SARS-CoV-2 can enter the brain by invading the olfactory bulb, by axonal transport from peripheral nerves, and by hematogenous pathways through the BBB [ 35 ]. SARS-CoV-2 could bind to ACE2 receptors on dopaminergic neurons, altering the rate of accumulation of misfolded α-synuclein, and promoting mitochondria stress, autophagy, and apoptosis [ 35 , 36 ]. Apart from the direct invasion of SARS-CoV-2 into the CNS, post-infection immune-mediated process also plays an important role in the development of PD [ 37 ].…”

“…Dopaminergic neurons are considered to be susceptible to SARS-CoV-2 infection since both ACE2 and TMPRSS2 receptors are overexpressed in the substantia nigra [ 76 , 77 ]. Under certain pathological circumstances, SARS-CoV-2 acts as a neurodegenerative enhancer to potentially drive the development or progression of PD and its related motor and non-motor symptoms [ 35 , 78 ]. In direct pathways, SARS-CoV-2 enters the CNS through the olfactory nerve via axonal transport from peripheral nerves, or through the BBB [ 79 ].…”

SARS-CoV-2, COVID-19 and Neurodegeneration

“…The potential pathophysiological or etiological impact of SARS-CoV-2 on PD is discussed in four review articles. Morowitz et al present a narrative review about the role of SARS-CoV-2 in modifying neurodegenerative processes in PD [ 5 ]. Drelich-Zbroja attempt to collate the existing scientific evidence regarding the possible role of SARS-CoV-2 in the pathophysiology of PD [ 6 ].…”