Texas Children’s investigator wins $2.4M grant for ALS research
Project looks at inflammation in neurodegenerative diseases
A Texas Children’s Hospital investigator has received a $2.4 million grant for a study that seeks to understand whether mechanisms used by bacteria to hide from the immune system can be explored to ease inflammation in amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.
Steven Boeynaems, PhD, an investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s and an assistant professor in molecular and human genetics at Baylor College of Medicine, received the National Institutes of Health NIH Director’s New Innovator Award, The award is part of the NIH Common Fund’s High-Risk, High-Reward Research program, which supports early-career investigators with research projects that have the potential for broad impact in areas that are important to the NIH mission.
Boeynaems’ research project will focus on neurodegenerative diseases such as ALS, a related condition called frontotemporal dementia (FTD), and Alzheimer’s disease. “Inflammation is involved in many other diseases, including autoimmune disease and cardiovascular disease,” he said in a university press release. “We believe that the concepts we are studying here are going to be applicable across many different types of disease.”
ALS research and inflammation
Inflammation contributes to cell damage in most neurodegenerative conditions. Researchers believe this to be at least in part triggered by astrocytes and microglia, which normally provide support to nerve cells but acquire a pro-inflammatory profile in these diseases.
The abnormal activation of astrocytes and microglia seems to correlate with the accumulation of misfolded protein clumps in the brain. In ALS, most cases are marked by the abnormal accumulation of the TDP-43 protein, which is also seen in about half of FTD and many Alzheimer’s patients.
Boeynaems previously found that some of the proteins that form toxic clumps mimic signals that activate the innate immune system, the first line of defense against microbes. The innate immune system includes microglia and many other immune cells.
“We are starting to understand that the protein pathology in the brain triggers neuroinflammation because it mimics the molecular features of an infection,” he said. “If you look at the structure of these proteins and how they interact with immune cells, it’s the same as how bacterial and viral proteins would interact.”
The research team will explore whether these protein clumps can indeed activate the immune system similarly to bacteria and viruses, providing a potential explanation for the way neuroinflammation develops.
If these toxic protein aggregates have similarities with infectious diseases in how they activate the immune system, it’s possible that mechanisms used by microbes to hide from the immune system can be used in neurodegenerative diseases to prevent the immune system from reacting to the protein clumps and causing inflammation.
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