The microglial innate immune protein PGLYRP1 mediates neuroinflammation and consequent behavioral changes

Anup Bhusal1, Jae-Hong Kim2, Seung-Chan Kim3

  • 1Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.

Cell Reports
|February 23, 2024
PubMed

Insights

Peptidoglycan recognition protein 1 (PGLYRP1) is upregulated in neuroinflammation and drives inflammatory responses. Targeting PGLYRP1 may offer new therapeutic strategies for brain inflammation.

Area of Science:

  • Neuroimmunology
  • Innate Immunity
  • Molecular Biology

Background:

  • Peptidoglycan recognition protein 1 (PGLYRP1) is crucial for antibacterial actions and innate immunity.
  • The role and expression of PGLYRP1 in neuroinflammatory conditions are not well understood.

Purpose of the Study:

  • To investigate the expression and function of PGLYRP1 in neuroinflammation.
  • To elucidate the molecular mechanisms by which PGLYRP1 influences neuroinflammation.

Main Methods:

  • Analysis of PGLYRP1 expression in inflamed human and mouse central nervous system tissue.
  • In vivo studies using recombinant PGLYRP1 and Pglyrp1 gene knockdown.
  • In vitro studies using cultured glial cells to identify interaction partners and signaling pathways.

Main Results:

  • PGLYRP1 is upregulated in inflamed brain and spinal cord, primarily in microglia.
  • Recombinant PGLYRP1 exacerbates neuroinflammation, reactive gliosis, and behavioral deficits in animal models.
  • PGLYRP1 promotes neuroinflammation via the TREM1-Syk-Erk1/2-Stat3 pathway in glial cells.
  • Pglyrp1 gene knockdown attenuates the inflammatory response.

Conclusions:

  • Microglial PGLYRP1 acts as a mediator of neuroinflammation.
  • PGLYRP1 represents a potential biomarker and therapeutic target for neuroinflammatory diseases.