Skip Navigation

ALS News

field with sun shining

Aug 9
2019

Research Bit: The role of microglia cells in ALS disease pathogenesis

Research Bits
The Packard Center welcomed Rita Sattler from Barrow Neurological Institute to a recent Investigator's Meeting.

Meeting Date: 9 August 2019

Presenter: Rita Sattler

Talk Title: The role of microglia cells in ALS disease pathogenesis

What was the question being asked?

Microglial, the resident immune cells of the brain and spinal cord, are responsible for synaptic pruning, a process that refines and edits neuronal circuits in the brain. Guided by specific cues (think airport marshall guiding a plane into position), microglia selectively trim away superfluous synapses to increase the efficiency of communication between neurons. This is a normal process that is essential to development of the healthy brain. However, when it occurs in an aberrant or excessive manner, synaptic pruning can drive the degenerative process that underlies dementia. The Sattler lab is seeking to understand how microglia contribute to the loss of synaptic connections between neurons in frontotemporal dementia (FTD). 

Why is this important for ALS research?

It has been known for some time that loss of neuronal synpases, the communication points between brain cells, is linked to neurodegenerative disease. However, the mechanisms underlying this process are poorly understood. It has been shown in models of Alzheimer’s disease (AD), that microglia cells are involved in this process but the extent to which they are involved in this process in ALS/FTD is unknown. Sattler’s work is aimed at unraveling this biology. 

What was the take-home message?

To date, the Sattler lab has successfully generated induced pluripotent stem cell (iPSC) derived cortical neurons and microglia, both of which express cell type specific proteins and are functionally active. iPSC derived cortical neurons and microglia both independently display alterations similar to those seen in FTD. The next steps of the study will bring cortical neurons and microglia together in the lab to determine whether microglia can initiate disease relevant changes in neuronal function.  

How do you think the results of this study might impact future approaches to the treatment of ALS? 

Most research focuses solely on the cell autonomous mechanisms of neuronal degeneration in disease. The research conducted by the Sattler lab employs a more complex cellular environment to evaluate both cell autonomous and non-cell autonomous contributions to disease pathogenesis. Ultimately, this work will increase our overall understanding of the mechanisms underlying neurodegeneration and in turn provide crucial knowledge towards the identification of therapeutic targets that otherwise may have been missed in model systems focused on one cell type. 

 

Alyssa Coyne, Ph.D.
Postdoctoral Fellow, Rothstein Lab
Johns Hopkins University School of Medicine
Department of Neurology

Sign up for our ALS Alert Newsletter
Sign Up