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Does SARS-CoV-2 affect neurodegenerative disorders? TLR2, a potential receptor for SARS-CoV-2 in the CNS

Journal

EXPERIMENTAL AND MOLECULAR MEDICINE
Volume 54, Issue 4, Pages 447-454

Publisher

SPRINGERNATURE
DOI: 10.1038/s12276-022-00755-7

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Funding

  1. Intramural Research Program of the National Institutes of Health, National Institute on Aging

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The interaction between the SARS-CoV-2 virus and the immune receptor TLR2 in the central nervous system (CNS) is implicated in the neurological symptoms of COVID-19. TLR2 plays a critical role in the response to SARS-CoV-2 infiltration into the CNS and may contribute to the development of neurodegenerative diseases. Understanding this link could help in developing new treatments for the neurological symptoms of COVID-19.
SARS-CoV-2: Receptor linked to the neurological toll of COVID-19 Interaction between the SARS-CoV-2 virus and a membrane protein in the central nervous system (CNS) that recognizes foreign substances is implicated in causing some of the neurological symptoms of COVID-19. Toll-like receptor 2 protein (TLR2) binds to components of microbes, including specific parts of the SARS-CoV-2 virus, as part of its role in natural immunity. It is widely present in many brain cells and is known to be involved in the pathogenesis of neurodegenerative diseases including Alzheimer's and Parkinson's diseases. Changyoun Kim, Eliezer Masliah and colleagues at the National Institutes of Health in Bethesda, USA, review the emerging evidence suggesting TLR2 plays a critical role in the response to SARS-CoV-2 virus infiltration into the CNS, inducing or accelerating neurological degeneration. Deeper understanding of the link could help develop new treatments for the neurological symptoms of COVID-19. The coronavirus (COVID-19) pandemic, caused by severe acute respiratory system coronavirus 2 (SARS-CoV-2), has created significant challenges for scientists seeking to understand the pathogenic mechanisms of SARS-CoV-2 infection and to identify the best therapies for infected patients. Although ACE2 is a known receptor for the virus and has been shown to mediate viral entry into the lungs, accumulating reports highlight the presence of neurological symptoms resulting from infection. As ACE2 expression is low in the central nervous system (CNS), these neurological symptoms are unlikely to be caused by ACE2-virus binding. In this review, we will discuss a proposed interaction between SARS-CoV-2 and Toll-like receptor 2 (TLR2) in the CNS. TLR2 is an innate immune receptor that recognizes exogenous microbial components but has also been shown to interact with multiple viral components, including the envelope (E) protein of SARS-CoV-2. In addition, TLR2 plays an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Based on these observations, we hypothesize that TLR2 may play a critical role in the response to SARS-CoV-2 infiltration in the CNS, thereby resulting in the induction or acceleration of AD and PD pathologies in patients.

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