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Targeting Progranulin as an Immuno-Neurology Therapeutic Approach.

Maria A Boylan1, Andrew Pincetic1, Gary Romano1

  • 1Alector, Inc., 131 Oyster Point Blvd, Suite 600, South San Francisco, CA 94080, USA.

International Journal of Molecular Sciences
|November 14, 2023
PubMed
Summary

Immuno-neurology harnesses the brain's immune system to combat neurodegenerative diseases like dementia. By targeting microglia dysfunction, this approach aims to restore brain health and function.

Keywords:
PGRNfrontotemporal dementiaimmuno-neurologyneuroimmunologyneuroinflammation

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Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • Microglia, the brain's immune cells, are crucial for neuronal support and surveillance.
  • Dysfunctional microglia, often due to progranulin (PGRN) deficiency, are linked to neurodegenerative diseases such as frontotemporal dementia (FTD-GRN), Alzheimer's disease (AD), Parkinson's disease (PD), and ALS.
  • Immuno-neurology offers a novel therapeutic strategy to address immune surveillance failure in the central nervous system (CNS).

Purpose of the Study:

  • To explore immuno-neurology as a therapeutic strategy for dementia and neurodegeneration.
  • To investigate the role of progranulin (PGRN) in microglial function and its association with neurodegenerative diseases.
  • To highlight the potential of immuno-neurology in modulating microglia to counteract neurodegenerative pathologies.

Main Methods:

  • Focus on targeting immune checkpoint-like proteins to modulate microglial function.
  • Investigating the impact of loss-of-function (LOF) mutations in the progranulin gene (GRN).
  • Reviewing ongoing clinical trials aimed at elevating PGRN levels.

Main Results:

  • Progranulin (PGRN) deficiency leads to microglial dysfunction and is associated with various neurodegenerative disorders.
  • Immuno-neurology interventions can potentially convert aging/dysfunctional microglia into disease-fighting cells.
  • These interventions may clear misfolded proteins, promote repair, and optimize neuronal function.

Conclusions:

  • Immuno-neurology represents a promising therapeutic avenue for neurodegenerative disorders.
  • Modulating microglia function through PGRN elevation or other immuno-neurology targets can counteract disease pathologies.
  • Successful immuno-neurology treatments could revolutionize neurodegenerative disease management by shifting the brain's immune state from inflammatory to homeostatic.