Targeting Brain Immune Cells as a Novel Therapeutic in Alzheimer's Disease

Principal Investigator

Co-Principal Investigator

  • Sourav  Ghosh, PhD

    Sourav Ghosh, PhD

    Yale University
    New Haven, CT

Project Goals

The project aim is to understand how a brain immune cell protein and novel therapy target offer protection against Alzheimer's disease.

Project Summary

Microglia are immune cells in the brain with an increasingly recognized role in Alzheimer's disease. Carla Rothlin, PhD, and her group have identified a microglial protein that seems to protect cells against the effects of Alzheimer's disease. Increased activity of the protein, called AXL, is linked to protection against cognitive decline in lab models of Alzheimer's disease.

Dr. Rothlin and her team hope to determine exactly what AXL does that offers this protection. Possibilities based on the known functions of AXL include a role in clearing out dead cells or amyloid-beta plaques that mark the condition or in preventing brain inflammation associated with Alzheimer's disease. 

To follow the process that leads to this protection, the team plans to use a series of lab models, each with one AXL function selectively disabled while retaining the others. In this way, Dr. Rothlin's group will sort out which AXL function offers protection against Alzheimer's disease and follow the sequence of events that leads up to more AXL production by microglia. 

AXL is a promising lead in part because drugs, including antibodies that target this class of proteins, have been being developed for many years. In addition, a natural molecule that activates AXL, known as GAS6, has already been identified, giving researchers a head start on finding ways to trigger AXL activity. The researchers expect the findings to highlight targets for such treatments that could modify or protect against Alzheimer's disease.

Publications

First published on: September 11, 2023

Last modified on: July 16, 2024