Both in the news and through personal connections with those afflicted, I feel as though the discussion of inflammation, and its correlation to autoimmune disorders, is an increasingly discussed topic in health. Some of this discussion is productive, as new research is constantly emerging to explain the mechanisms of these autoimmune disorders and certain neuroprotective factors that provide hope into novel treatment developments. However, it is my opinion that much of the conversation around the increasingly pseudoscientific field of inflammation is distracting and dangerous towards evidence-based prevention and treatment. Dr. Yanan Chen’s recent talk on oligodendrocyte regeneration in inflammatory conditions like MS has sparked two main interests: 1) What does it take to protect the brain’s myelin in the face of chronic immune stress, and 2) why is MS, as well as many other autoimmune conditions, much more prevalent in women? As a white male entering the neuroscience field, I believe it is my responsibility to educate myself and others, as well as progress the intent and methods of research, to reflect some of the sociological factors that I discovered in some of the articles referenced in this blog.
First, taking a look at Dr. Chen’s work, we can understand how two molecules called Sephin1 and bazedoxifene (BZA) support oligodendrocyte survival and remyelination under inflammatory conditions like MS. Sephin1 prolongs the integrated stress response (ISR), giving cells time to recover by slowing protein production, while BZA promotes the maturation of oligodendrocyte precursor cells. Her work shows how when they work together, they create a more resilient environment for myelin repair. This approach is supported by a 2021 study by Lin et al titled “Endoplasmic reticulum stress modulator Sephin1 facilitates myelin regeneration” which showed that enhancing ISR in mice led to stronger remyelination and better protection of oligodendrocytes. Both papers discuss the cellular stress mechanisms at play in MS. Understanding processes like eIF2α phosphorylation and stress granule formation may be key to developing therapies that don’t just suppress inflammation, but actively protect the brain’s repair systems.
A 2024 study from Stanford, published in Cell by Kotzin et al, identified a gene expressed from the second X chromosome that escapes typical silencing and may drive the overactive immune responses seen in many autoimmune diseases. This finding offers an explanation for why conditions like MS disproportionately affect women, which was something Dr. Chen also emphasized in her talk when she highlighted how MS affects women at three times the rate of men. Other conditions like lupus, rheumatoid arthritis, and Hashimoto’s thyroiditis show similar disproportion representations. This leads me to want to understand how these biological disparities intersect with historical gaps in research and care. If women are more genetically predisposed to autoimmune overactivation, how much of their disproportionate burden is compounded by systemic issues? Recognizing these patterns should shape how we prioritize funding, structure clinical trials, and build more inclusive models of neurological disease. Immune-related chronic illnesses are multifactorial, so understanding the biology is important, but social epidemiology should also play a large role in how we approach future MS treatment and prevention.
Approaching MS and other autoimmune diseases requires understanding cellular pathways and mechanisms, but it also must include examining clinical practices and societal structures that shape who gets sick. For me, this topic has reinforced the importance of conducting neuroscience research that upholds bioethical principles and reflects the lived realities of those most affected.
References
Chen, Y., Quan, S., Patil, V., Kunjamma, R. B., Tokars, H. M., Leisten, E. D., Joy, G., Wills, S., Chan, J. R., Wong, Y. C., & Popko, B. (2023). Insights into the mechanism of oligodendrocyte protection and remyelination enhancement by the integrated stress response. Glia, 71(9), 2180–2195. https://doi.org/10.1002/glia.24386
Lin, Y., Huang, G., Jamison, S., Li, J., Harding, H. P., Ron, D., & Popko, B. (2021). Endoplasmic reticulum stress modulator Sephin1 facilitates myelin regeneration. eLife, 10, e61270. https://doi.org/10.7554/eLife.61270
Kotzin, J. J., Spencer, S. P., McCright, S. J., Kumar, D. B. U., Collet, M. A., Mowel, W. K., Elliott, E. N., Uyar, A., Dunagin, M., & Williams, A. (2024). Escape from X-inactivation predisposes females to autoimmune disease. Cell, 187(3), 596–612.e18. https://doi.org/10.1016/j.cell.2024.01.003
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