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Your Environment. Your Health.

Astrocytes' Role in Inflammation and Neurodegeneration

Francisco Quintana, Ph.D.
Harvard Medical School
R01ES025530, R01ES029136

NIEHS grantees identified a novel pathway that controls the metabolic response of astrocytes, which may explain how they are involved in inflammation and neurodegeneration. Astrocytes are brain and spinal cord cells essential to maintaining central nervous system (CNS) health, performing functions such as providing nerve cells with nutrients. However, they have also been linked to promoting CNS inflammation and contributing to multiple sclerosis (MS) development.

Using a mouse model of MS, researchers examined the role of astrocytes and found that during the progressive phase of the disease, astrocytes in the brain switched on metabolic pathways that activated a specific protein found in the mitochondria of cells known as mitochondrial antiviral signaling (MAVS) protein. This led to activation of several pro-inflammatory genes, triggering inflammation in the brain and spinal cord. At the same time, astrocytes began to produce less lactate, which provides metabolic support to cells, and provided less of it to the nerve cells.

Researchers tested if these metabolic pathways were blocked by treating mice with miglustat, a drug used to treat two rare metabolic disorders. Miglustat given to mice before the onset of MS effectively suppressed MAVS activation and subsequent inflammation.

According to the authors, the findings outline a new role for MAVS in CNS inflammation and a potential therapeutic target for MS. Because MAVS is also activated in response to viruses, the authors noted that these findings could offer insights into the ways in which viruses that are considered possible triggers of MS might contribute to the disease.

Citation: Chao CC, Gutierrez-Vazquez C, Rothhammer V, Mayo L, Wheeler MA, Tjon EC, Zandee SEJ, Blain M, de Lima KA, Takenaka MC, Avila-Pacheco J, Hewson P, Liu L, Sanmarco LM, Borucki DM, Lipof GZ, Trauger SA, Clish CB, Antel JP, Prat A, Quintana FJ. 2019. Metabolic control of astrocyte pathogenic activity via cPLA2-MAVS. Cell 179(7):1483–1498.e22.

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