2023 Endolysosomal Activity in Alzheimer’s (E2A)
SHIP1 Agonism and Lipid Burden in Alzheimer's Disease
Are there ways to support clearance of waste in the brain?
William Garrow Kerr, Ph.D.
SUNY Upstate Medical University
Syracuse, NY - United States
Background
Microglia are the primary immune cells in the brain that serve as one of the first defenses in the brain. Microglia sense and help remove unwanted proteins from the brain, in part through a process called phagocytosis, during which the microglial cells engulf (or “swallow”) the unwanted proteins. Microglia then deliver the unwanted proteins to a lysosome, where it is broken down and cleared. Studies suggest that in brain diseases, such as Alzheimer’s, this waste disposal system becomes impaired and is unable to properly clear waste from the brain. Understanding the basic biology of this system could reveal new ways to promote the clearance of waste in the brain, including the beta-amyloid protein plaques that are a hallmark of Alzheimer’s.
Research Plan
Dr. William Kerr has been developing compounds that target the waste disposal system of microglia. The researchers will test these compounds on a specialized type of stem cell collected from adult human tissue called human induced pluripotent stem cells (hiPSCs). These are adult human skin cells that can be “reprogrammed” into any type of cell, including microglia, and grown in laboratory dishes. The team will test these compounds on the microglia to see whether they may activate the waste removal system. The researchers will also work to identify which genes are turned on by these compounds when the system is activated.
Impact
These findings will clarify the basic biology of the brain’s system of clearing waste, and whether this system may be a potential therapeutic target for Alzheimer’s.