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Specialized Pro-Resolving Lipid Mediators: Emerging Therapeutic Candidates for Multiple Sclerosis

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Abstract

Multiple sclerosis (MS) is a neuroinflammatory disease in which unresolved and uncontrolled inflammation disrupts normal cellular homeostasis and leads to a pathological disease state. It has long been recognized that endogenously derived metabolic by-products of omega fatty acids, known as specialized pro-resolving lipid mediators (SPMs), are instrumental in resolving the pathologic inflammation. However, there is minimal data available on the functional status of SPMs in MS, despite the fact that MS presents a classical model of chronic inflammation. Studies to date indicate that dysfunction of the SPM biosynthetic pathway is responsible for their altered levels in patient-derived biofluids, which contributes to heightened inflammation and disease severity. Collectively, current findings suggest the contentious role of SPMs in MS due to variable outcomes in biological matrices across studies conducted so far, which could, in part, also be attributed to differences in population characteristics. It seems that SPMs have neuroprotective action on MS by exerting proresolving effects on brain microglia in its preclinical model; however, there are no reports demonstrating the direct effect of SPMs on oligodendrocytes or neurons. This reveals that “one size does not fit all” notion holds significance for MS in terms of the status of SPMs in other inflammatory conditions. The lack of clarity served as the impetus for this review, which is the first of its kind to summarize the relevant data regarding the role of SPMs in MS and the potential to target them for biomarker development and future alternative therapies for this disease. Understanding the mechanisms behind biological actions of SPMs as resolution mediators may prevent or even cure MS and other neurodegenerative pathologies.

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Acknowledgments

Dr. Insha Zahoor is highly indebted to her family for being extraordinarily supportive through every odd of life and handling every worst situation when she was not available for them. It takes many sacrifices at the family level to pursue a career in research, especially for a caregiver. I dedicate this piece of writing to my little brother Imran Zahoor (Imu) who is suffering from seizure disorder with mental retardation and a plethora of psychiatric ailments. In serving as a caregiver for him, I have realized the impact that effective therapeutic research interventions can make on the life of a patient and his caregivers.

The authors thank Prof. Charles N. Serhan, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA, for his valuable suggestions while reviewing this manuscript.

Funding

This work was supported by the National Multiple Sclerosis Society (US) Research Grant (RG-1807-31964), the US National Institutes of Health Grant (R01 NS112727, AI144004), and Henry Ford Hospital Internal Grant (A10270) to SG. The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.

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  1. Department of Neurology, Research Division, Education & Research Building, Henry Ford Hospital, Room 4023, 2799 W Grand Blvd, Detroit, MI, 48202, USA

    Insha Zahoor

  2. Department of Neurology, Research Division, Education & Research Building, Henry Ford Hospital, Room 4051, 2799 W Grand Blvd, Detroit, MI, 48202, USA

    Shailendra Giri

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Both IZ and SG conceived the idea for the paper. IZ performed the literature search, and data analysis and compiled the manuscript. SG provided helpful suggestions in the preparation of this manuscript and reviewed the draft before approval for publication.

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Correspondence to Insha Zahoor or Shailendra Giri.

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Zahoor, I., Giri, S. Specialized Pro-Resolving Lipid Mediators: Emerging Therapeutic Candidates for Multiple Sclerosis. Clinic Rev Allerg Immunol 60, 147–163 (2021). https://doi.org/10.1007/s12016-020-08796-4

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