Possible Link between SARS-CoV-2 Infection and Parkinson’s Disease: The Role of Toll-Like Receptor 4

Abstract

Parkinson’s disease (PD) is the most common neurodegenerative motor disorder characterized by selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the midbrain, depletion of dopamine (DA), and impaired nigrostriatal pathway. The pathological hallmark of PD includes the aggregation and accumulation α-synuclein (α-SYN). Although the precise mechanisms underlying the pathogenesis of PD are still unknown, the activation of toll-like receptors (TLRs), mainly TLR4 and subsequent neuroinflammatory immune response, seem to play a significant role. Mounting evidence suggests that viral infection can concur with the precipitation of PD or parkinsonism. The recently identified coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of ongoing pandemic coronavirus disease 2019 (COVID-19), responsible for 160 million cases that led to the death of more than three million individuals worldwide. Studies have reported that many patients with COVID-19 display several neurological manifestations, including acute cerebrovascular diseases, conscious disturbance, and typical motor and non-motor symptoms accompanying PD. In this review, the neurotropic potential of SARS-CoV-2 and its possible involvement in the pathogenesis of PD are discussed. Specifically, the involvement of the TLR4 signaling pathway in mediating the virus entry, as well as the massive immune and inflammatory response in COVID-19 patients is explored. The binding of SARS-CoV-2 spike (S) protein to TLR4 and the possible interaction between SARS-CoV-2 and α-SYN as contributing factors to neuronal death are also considered.

Comparison of COVID-19 characteristics in Egyptian patients according to their Toll-Like Receptor-4 (Asp299Gly) polymorphism

“…Also, TLR-4 (Asp299Gly) polymorphism has been linked to bacterial pneumonia susceptibility, probably due to weakened first-line defensive mechanisms [17]. Many studies conducted during the COVID-19 pandemic pointed to the importance of TLR-4 in mounting an effective immune response to SARS-CoV-2 [9,[18][19][20][21].…”

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

“…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.…”

Toll-Like Receptor 4 Polymorphisms (896A/G and 1196C/T) as an Indicator of COVID-19 Severity in a Convenience Sample of Egyptian Patients

“…5 Several studies conducted during the COVID-19 pandemic have found that dysregulated TLR-4 signaling may contribute to the initial failure of viral clearance and the development of COVID-19 severe clinical symptoms, namely adult respiratory distress syndrome (ARDS) and lethal respiratory failure. [5][6][7][8][9] Considering the importance of TLR-4 in initiating innate immunity against SARS-CoV-2, it is supposed that genetic heterogeneity in the TLR-4 gene might explain, at least in part, the broad spectrum of COVID-19 manifestations. Therefore, in this study, we assessed two common TLR-4 single nucleotide polymorphisms (SNPs), Asp299Gly and Thr399Ile, in Egyptian patients with COVID-19 and evaluated their frequency concerning disease severity, progression, and cytokine storm.…”