Role of brain inflammation in Alzheimer’s and Parkinson’s may depend on the behavior of microglia

Researchers from the Alzheimer’s Center at Temple (ACT) provide new insights into how microglia, the brain’s immune cells, exhibit an apparent dual function with the ability to both increase and decrease inflammation in the brain. Deeper understanding of this phenomenon could shape the potential for identifying the causes of, and possible treatment for neurodegenerative diseases including Alzheimer’s disease and Parkinson’s.

The analysis, described in a new paper, “Dual Role of Microglia in Neuroinflammation and Neurodegenerative Diseases,” has been published in the journal Neurobiology of Disease.

Senior author Dr. Domenico Praticò, M.D., the Scott Richards North Star Foundation Chair for Alzheimer’s Research, Professor of Neural Sciences at the Alzheimer’s Center at Temple (ACT), in the Lewis Katz School of Medicine at Temple University (LKSOM), along with lead author Amir Ajoolabady, Temple University, have coordinated the review with international collaborators working in China, South Korea, and Saudi Arabia.

Microglia are key regulators of the brain’s immune system. Under healthy conditions, they maintain homeostasis by clearing waste and protecting neurons. But in disease, these same cells can become overactivated, driving chronic inflammation and contributing to neuronal loss.

“Microglia are a double-edged sword,” says Dr. Domenico Praticò. “On one hand, they can suppress inflammation and promote brain repair; on the other, they can amplify neuroinflammatory damage. Understanding the molecular switches that control this behavior could open the door to entirely new therapeutic strategies for neurodegenerative diseases.”

The review highlights recent research on two crucial proteins that influence microglial function, TREM2 (Triggering Receptor Expressed on Myeloid Cells 2), which supports microglial survival and debris clearance, and HMGB1 (High Mobility Group Box 1), which promotes inflammation when released from damaged cells.

Together, these molecules form part of a complex signaling network that determines whether microglia act as protectors or aggressors in the brain.

“Our goal is to pinpoint molecular targets that can shift microglia toward a neuroprotective state,” Dr. Praticò explains. “By modulating these pathways, we hope to develop new treatments that not only slow disease progression but also preserve cognitive function.”

Further research into the dual behavior of microglia could extend beyond Alzheimer’s and Parkinson’s, with implications for diseases like multiple sclerosis and other conditions involving chronic brain inflammation.

Researchers from the Alzheimer’s Center at Temple (ACT) provide new insights into how microglia, the brain’s immune cells, exhibit an apparent dual function with the ability to both increase and decrease inflammation in the brain. Deeper understanding of this phenomenon could shape the potential for identifying the causes of, and possible treatment for neurodegenerative diseases including Alzheimer’s disease and Parkinson’s.

The analysis, described in a new paper, “Dual Role of Microglia in Neuroinflammation and Neurodegenerative Diseases,” has been published in the journal Neurobiology of Disease.

Senior author Dr. Domenico Praticò, M.D., the Scott Richards North Star Foundation Chair for Alzheimer’s Research, Professor of Neural Sciences at the Alzheimer’s Center at Temple (ACT), in the Lewis Katz School of Medicine at Temple University (LKSOM), along with lead author Amir Ajoolabady, Temple University, have coordinated the review with international collaborators working in China, South Korea, and Saudi Arabia.

Microglia are key regulators of the brain’s immune system. Under healthy conditions, they maintain homeostasis by clearing waste and protecting neurons. But in disease, these same cells can become overactivated, driving chronic inflammation and contributing to neuronal loss.

“Microglia are a double-edged sword,” says Dr. Domenico Praticò. “On one hand, they can suppress inflammation and promote brain repair; on the other, they can amplify neuroinflammatory damage. Understanding the molecular switches that control this behavior could open the door to entirely new therapeutic strategies for neurodegenerative diseases.”

The review highlights recent research on two crucial proteins that influence microglial function, TREM2 (Triggering Receptor Expressed on Myeloid Cells 2), which supports microglial survival and debris clearance, and HMGB1 (High Mobility Group Box 1), which promotes inflammation when released from damaged cells.

Together, these molecules form part of a complex signaling network that determines whether microglia act as protectors or aggressors in the brain.

“Our goal is to pinpoint molecular targets that can shift microglia toward a neuroprotective state,” Dr. Praticò explains. “By modulating these pathways, we hope to develop new treatments that not only slow disease progression but also preserve cognitive function.”

Further research into the dual behavior of microglia could extend beyond Alzheimer’s and Parkinson’s, with implications for diseases like multiple sclerosis and other conditions involving chronic brain inflammation.