Targeting the NLRX1 Pathway for Neuroprotection in Multiple Sclerosis: Marjan Gharagozloo, PhD

WATCH TIME: 5 minutes

"The takeaway message of this experiment is if we can target this pathway, activate the NLRX1 function, with some compounds, maybe we can slow down the neurodegeneration and activation of innate immune cells in the [central nervous system]."

Persistent activation of the innate immune system in the central nervous system is widely suspected as a critical factor in the progression of multiple sclerosis (MS) that leads to neurodegeneration. Unraveling the intricate mechanisms of reactive and inflammatory responses of glial cells may hold pivotal significance for novel neuroprotective interventions against the disease. NLRX1, a mitochondrial sensor of the innate immune system, negatively regulates several inflammatory pathways, which may offer a potential therapeutic avenue in MS progression.

In a recent study, investigators explored the role of NLRX1 in preventing inflammatory neurodegeneration in experimental models of MS. The preclinical data showed that NLRX1 prevented inflammatory neurodegeneration in experimental models of MS.¹ Presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 29 to March 2, in West Palm Beach, Florida, by senior author Marjan Gharagozloo, PhD, the findings suggest NLRX1 plays a neuroprotective role in inflammatory neurodegeneration which may occur through downregulation of inflammatory-reactive microglia and astrocytes.¹

Gharagozloo, assistant professor of neurology at Johns Hopkins Medicine, sat down with NeurologyLive® at the forum to discuss how the absence of NLRX1 relates to neurodegeneration in animal models. She also talked about the observed effects of activating T cells in lymphocyte-deficient mice. Additionally, Gharagozloo spoke about how promising the preliminary results with NLRX1 agonist are in terms of neuroprotection.

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REFERENCES
1. Gill J, Garton T, Smith MD, et al. Innate Immune Regulator NLRX1 Protects the Anterior Visual Pathway Against Inflammatory Neurodegeneration. Presented at ACTRIMS Forum 2024; February 29 to March 2; West Palm Beach, Florida. CE1.2.