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Author Spotlight: Advancing Rapid Detection of Respiratory Pathogens Using Microfluidic Chip

Published on: March 29, 2024

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Infectious Diseases

Herman Li1,2, Niccolò Terrando3,4,5, Harris A Gelbard6,7,8,9

  • 1Center for Neurotherapeutics Discovery, Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.

Advances in Neurobiology
|August 29, 2024
PubMed

Insights

Peripheral inflammation from infections like COVID-19 can harm the brain, affecting microglia. Targeting MLK3 and LRRK2 pathways may treat neurological issues in post-acute sequelae of COVID-19 (PASC) and HIV-associated neurocognitive disorders (HAND).

Area of Science:

  • Neuroimmunology
  • Infectious Disease Neurology
  • Neuroinflammation

Background:

  • Microglia, the brain's immune cells, are implicated in neurodegeneration and can sustain inflammation post-infection.
  • Peripheral inflammation, as seen in COVID-19, impacts the neuroimmune environment, leading to microgliosis.
  • Lessons from HIV-1 associated neurocognitive disorders (HAND) inform understanding of chronic neuroinflammation.

Purpose of the Study:

  • To discuss how SARS-CoV-2 infection causes neuroinflammation and post-acute sequelae of COVID-19 (PASC).
  • To explore the role of microglia in PASC and HAND pathogenesis.
  • To identify therapeutic targets for PASC and HAND.

Main Methods:

  • Review of current literature on microglial function in neurodegenerative and infectious diseases.
  • Analysis of the impact of SARS-CoV-2 on neurovascular and neuroimmune pathways.
  • Examination of the role of mixed lineage kinase 3 (MLK3) and leucine-rich repeat kinase (LRRK2) in inflammatory pathways.

Main Results:

  • Pulmonary SARS-CoV-2 infection can induce neurovascular and neuroimmune inflammation, contributing to PASC.
  • Microglial dysfunction, exacerbated by peripheral inflammation, plays a critical role in PASC and HAND.
  • MLK3 and LRRK2 are identified as key regulators of inflammatory and apoptotic pathways relevant to PASC and HAND pathogenesis.

Conclusions:

  • Targeting MLK3 and LRRK2 pathways offers a synergistic therapeutic strategy for both PASC and HAND.
  • Understanding microglial responses to viral infections is crucial for treating associated neurological complications.
  • Combined antiretroviral therapies (cART) for HIV highlight the long-term impact of managing peripheral infections on neurocognitive health.
Keywords:
Coronavirus disease 2019Human immunodeficiency virusHuman immunodeficiency virus-associated neurocognitive disorderInflammationLeucine-rich repeat kinase 2MicrogliaMixed lineage kinase 3Postacute sequelae of coronavirus disease 2019Severe acute respiratory syndrome coronavirus 2

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