Role of Toll-Like Receptors in Post-COVID-19 Associated Neurodegenerative Disorders?

Senthil Kumaran Satyanarayanan ¹ Tsz Fung Yip ² Zixu Han ¹ Huachen Zhu ² Dajiang Qin ^3* Suki Man Yan Lee ^1*

• ¹ Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong Science Park, Hong Kong SAR, China, Hong Kong, Hong Kong, SAR China
• ² School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China, Hong Kong, Hong Kong, SAR China
• ³ Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China, Guanzhou, China

In the intricate realm of interactions between hosts and pathogens, Toll-like receptors (TLRs), which play a crucial role in the innate immune response, possess the ability to identify specific molecular signatures. This includes components originating from pathogens such as SARS-CoV-2, as well as the resulting damage-associated molecular patterns (DAMPs), the endogenous molecules released after cellular damage. A developing perspective suggests that TLRs play a central role in neuroinflammation, a fundamental factor in neurodegenerative conditions like Alzheimer's and Parkinson's disease (PD). This comprehensive review consolidates current research investigating the potential interplay between TLRs, their signaling mechanisms, and the processes of neurodegeneration following SARS-CoV-2 infection with an aim to elucidate the involvement of TLRs in the long-term neurological complications of COVID-19 and explore the potential of targeting TLRs as a means of implementing intervention strategies for the prevention or treatment of COVID-19-associated longterm brain outcomes.receptor as a novel anti-amyloid therapeutic for Alzheimer's disease.