Maresin-1 promotes neuroprotection and modulates metabolic and inflammatory responses in disease-associated cell types in preclinical models of Multiple Sclerosis
Recommended Citation
Zahoor I, Nematullah M, Ahmed ME, Fatma M, Sajad M, Ayasolla K, Cerghet M, Palaniyandi S, Ceci V, Carrera G, Buttari F, Centonze D, Mao-Draayer Y, Rattan R, Chiurchiù V, and Giri S. 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; 108226.
Document Type
Article
Publication Date
1-24-2025
Publication Title
The Journal of biological chemistry
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 (RR-EAE) 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 (CNS). 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 RR-EAE 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 PBMCs substantiated the protective role of MaR1, expanding the therapeutic spectrum of SPMs. Altogether, these findings suggest the potential of MaR1 as a novel therapeutic agent for MS and other autoimmune diseases.
PubMed ID
39864620
ePublication
ePub ahead of print
First Page
108226
Last Page
108226
