2. Academic Validation
  3. Maresin-1 promotes neuroprotection and modulates metabolic and inflammatory responses in disease-associated cell types in preclinical models of multiple sclerosis

Maresin-1 promotes neuroprotection and modulates metabolic and inflammatory responses in disease-associated cell types in preclinical models of multiple sclerosis

  • J Biol Chem. 2025 Mar;301(3):108226. doi: 10.1016/j.jbc.2025.108226.
Insha Zahoor 1,  Mohammad Nematullah 1,  Mohammad Ejaz Ahmed 1,  Mena Fatma 1,  Mir Sajad 1,  Kameshwar Ayasolla 1,  Mirela Cerghet 1,  Suresh Palaniyandi 2,  Veronica Ceci 3,  Giulia Carrera 4,  Fabio Buttari 5,  Diego Centonze 5,  Yang Mao-Draayer 6,  Ramandeep Rattan 7,  Valerio Chiurchiù 3,  Shailendra Giri 8
Affiliations

Affiliations

  • 1 Department of Neurology, Henry Ford Health, Detroit, Michigan, USA.
  • 2 Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health, Detroit, Michigan, USA; Department of Physiology, Wayne State University, Detroit, Michigan, USA.
  • 3 Institute of Translational Pharmacology, National Research Council, Rome, Italy; Laboratory of Resolution of Neuroinflammation, IRCCS Santa Lucia Foundation, Rome, Italy.
  • 4 Laboratory of Resolution of Neuroinflammation, IRCCS Santa Lucia Foundation, Rome, Italy.
  • 5 Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Unit of Neurology, IRCCS Neuromed, Pozzilli (Is), Italy.
  • 6 Oklahoma Medical Research Foundation, Oklahoma, Farmington Hills, Michigan, USA.
  • 7 Women's Health Services, Henry Ford Health, Detroit, Michigan, USA.
  • 8 Department of Neurology, Henry Ford Health, Detroit, Michigan, USA. Electronic address: sgiri1@hfhs.org.
PMID: 39864620 DOI: 10.1016/j.jbc.2025.108226
Abstract

Multiple sclerosis (MS) is a prevalent inflammatory neurodegenerative disease in young people, causing neurological abnormalities and impairment. To investigate a novel therapeutic agent for MS, we observed the impact of maresin 1 (MaR1) on disease progression in a well-known, relapsing-remitting experimental autoimmune encephalomyelitis mouse model. Treatment with MaR1 accelerated inflammation resolution, reduced neurological impairment, and delayed disease development by reducing immune cell infiltration (CD4+IL-17+ and CD4+IFNγ+) into the central nervous system. Furthermore, MaR1 administration enhanced IL-10 production, primarily in macrophages and CD4+ cells. However, neutralizing IL-10 with an anti-IL-10 antibody eliminated the protective impact by MaR1 in relapsing-remitting experimental autoimmune encephalomyelitis model, implying the significance of IL-10 in MaR1 treatment. Metabolism has been recognized as a critical mediator of effector activity in many types of immune cells. In our investigation, MaR1 administration significantly repaired metabolic dysregulation in CD4+ cells, macrophages, and microglia in EAE mice. Furthermore, MaR1 treatment restored defective efferocytosis in treated macrophages and microglia. MaR1 also preserved myelin in EAE mice and regulated O4+ oligodendrocyte metabolism by reversing metabolic dysregulation via increased mitochondrial activity and decreased glycolysis. Overall, in a preclinical MS animal model, MaR1 therapy has anti-inflammatory and neuroprotective properties. It also induced metabolic reprogramming in disease-associated cell types, increased efferocytosis, and maintained myelination. Moreover, our data on patient-derived peripheral blood mononuclear cells substantiated the protective role of MaR1, expanding the therapeutic spectrum of specialized proresolving lipid mediators. Altogether, these findings suggest the potential of MaR1 as a novel therapeutic agent for MS and Other autoimmune diseases.

Keywords

DHA; EAE; IL-10; MS; Maresin1; Metabolism; SCENITH; SPM; inflammation; resolution; therapeutics.

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