Keywords
1. Neuronal Nogo Receptor 1
2. Axonal Transport
3. Experimental Autoimmune Encephalomyelitis
4. Inflammatory Demyelination
5. Neuroscience Research
An unprecedented advancement in the field of neuroscience highlights a promising direction in the combat against multiple sclerosis (MS), a debilitating autoimmune disorder affecting millions worldwide. Researchers have unveiled a considerably impactful strategy that targets the Neuronal Nogo Receptor 1 (NgR1) signaling pathway, which plays a pivotal role in preserving axonal transport and hindering inflammatory demyelination—the two characteristic features of MS. This revelation is developed over a series of explorative and conclusive studies grounded in molecular biology and neuroscience. (DOI: 10.1523/JNEUROSCI.1760-18.2019)
The Journal of Neuroscience recently published a groundbreaking research article stating that the limitation of NgR1 signaling during Experimental Autoimmune Encephalomyelitis (EAE) preserves axonal transport and abrogates inflammatory demyelination, an experimental model of MS. The in-depth study is authored by a team of international scientists, including prominent researchers Lee Jae Young JY, Kim Min Joung MJ, and Petratos Steven S – whose joint efforts have led to a potentially transformative approach in MS treatment.
Multiple sclerosis is known for the immune system’s erroneous attack on the protective sheath—myelin—that surrounds nerve fibers. This battle causes communication problems between the brain and the rest of the body and, in time, can lead to nerve deterioration or permanent damage. Symptoms range in severity and encompass physical, mental, and psychiatric problems.
However, central to the study in question is the NgR1 signaling pathway, the crux of the researchers’ investigative efforts. NgR1 forms part of a protein group critical for the regulation of axon growth and the maintenance of the myelin sheath. In the past, interfering with NgR1 functionality has shown to stimulate regrowth of nerve fibers in animal models (Akbik, FV et al., 2013).
The study in The Journal of Neuroscience (DOI: 10.1523/JNEUROSCI.1760-18.2019) utilizes murine models with a disabled NgR1 function either genetically (ngr1-/-) or through pharmaceutical means. The results were astounding in both instances; there was a remarkable preservation of axonal transport mechanisms—the process critically needed for the movement of proteins and organelles within the neuron—and a significant reduction in inflammatory demyelination.
Utilizing electron microscopy and various molecular biology techniques, the researchers meticulously detailed how the manipulation of NgR1 led to these favorable outcomes. In ngr1-/- mice and those where NgR1 was pharmacologically impaired, there was less axon degeneration, and a distinct preservation of retinal ganglion cells (RGCs) was observed. This was also supported by modulation effects on the collapsin response mediator protein-2 and kinesin, both vital for axon health (Arimura, N et al., 2005; Hares, K et al., 2017).
Given that EAE in rodents closely mirrors human MS in terms of its pathological process (Bjartmar, C et al., 2001), the implications of this research are profound. The approach could be a new therapeutic avenue to reign in the progressive and often unpredictable bouts of MS flare-ups. By impeding destructive mechanisms through the regulation of NgR1, we could stall the progression of the disease and mitigate both myelin damage and subsequent neurological deficits.
The significance of this research provides hope for a future wherein MS can be managed much more effectively. Decelerating or even preventing the progression of MS could significantly improve the quality of life for those afflicted by the disease, possibly allowing them to maintain employment, social connections, and a degree of normalcy that the condition often robs.
References
1. Akbik FV, Bhagat SM, Patel PR, Cafferty WB, Strittmatter SM (2013) Anatomical plasticity of adult brain is titrated by nogo receptor 1. Neuron 77:859–866. DOI: 10.1016/j.neuron.2012.12.027
2. Arimura N, Ménager C, Kawano Y, Yoshimura T, Kawabata S, Hattori A, Fukata Y, Amano M, Goshima Y, Inagaki M, Morone N, Usukura J, Kaibuchi K (2005) Phosphorylation by rho kinase regulates CRMP-2 activity in growth cones. Mol Cell Biol 25:9973–9984. DOI: 10.1128/MCB.25.22.9973-9984.2005
3. Bjartmar C, Kinkel RP, Kidd G, Rudick RA, Trapp BD (2001) Axonal loss in normal-appearing white matter in a patient with acute MS. Neurology 57:1248–1252. DOI: 10.1212/WNL.57.7.1248
4. Hares K, Redondo J, Kemp K, Rice C, Scolding N, Wilkins A (2017) Axonal motor protein KIF5A and associated cargo deficits in multiple sclerosis lesional and normal-appearing white matter. Neuropathol Appl Neurobiol 43:227–241. DOI: 10.1111/nan.12305
5. Lee JY, Kim MJ, Li L, Velumian AA, Aui PM, Fehlings MG, Petratos S (2017) Nogo receptor 1 regulates caspr distribution at axo-glial units in the central nervous system. Sci Rep 7:8958. DOI: 10.1038/s41598-017-09405-9
In conclusion, this research possesses the potential to propel us into a new age for MS treatment, one in which the debilitating progression of the disease may be tempered. As these results inspire further clinical trials and broadened research, the hope is that a new, effective therapy for MS is in sight. While the researchers caution that much work lies ahead to convert these findings into a clinical reality, the study unequivocally represents a significant step forward in the journey towards a cure for multiple sclerosis.