Vitamin B12 provides neuroprotection in multiple sclerosis
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For decades, scientists have noted an intriguing similarity between a deficiency in vitamin B12 – an essential nutrient that supports healthy development and functioning of the central nervous system (CNS) – and multiple sclerosis (MS), a chronic disease in which the body’s immune system attacks the CNS and which can produce neurodegeneration.
Both vitamin B12 (also known as cobalamin) deficiency and MS produce similar neurological symptoms, including numbness or tingling in hands and feet, vision loss, difficulty walking or speaking normally and cognitive dysfunction, such as problems with memory.
In a new study, published in Cell Reports, researchers describe a novel molecular link between vitamin B12 and MS that takes place in astrocytes – important non-neuronal glial cells in the brain.
“The shared molecular binding of the brain’s vitamin B12 carrier protein, known as transcobalamin 2 or TCN2, with the FDA-approved MS drug fingolimod provides a mechanistic link between B12 signaling and MS, towards reducing neuroinflammation and possibly neurodegeneration,” said the author.
“Augmenting brain B12 with fingolimod or potentially related molecules could enhance both current and future MS therapies.”
In their paper, the team focused on the molecular functioning of FTY720 or fingolimod (Gilenya®), a sphingosine 1-phosphate (S1P) receptor modulator that suppresses distribution of T and B immune cells errantly attacking the brains of MS patients.
Working with an animal model of MS as well as human post-mortem brains, the researchers found that fingolimod suppresses neuroinflammation by functionally and physically regulating B12 communication pathways, specifically elevating a B12 receptor called CD320 needed to take up and use needed B12 when it is bound to TCN2, which distributes B12 throughout the body, including the CNS. This known process was newly identified for its interactions with fingolimod within astrocytes. Importantly, the relationship was also observed in human MS brains.
Of particular note, the researchers reported that lower levels of CD320 or dietary B12 restriction worsened the disease course in an animal model of MS and reduced the therapeutic efficacy of fingolimod, which occurred through a mechanism in which fingolimod hitchhikes by binding to the TCN2-B12 complex, allowing delivery of all to the astrocytes via interactions with CD320, with component losses disrupting the process and worsening disease.
These new findings further support to the use of B12 supplementation – especially in terms of delivering the vitamin to astrocytes within the brain – while revealing that fingolimod can correct the impaired astrocyte-B12 pathway in people with MS.
The scientists said it is possible that other S1P receptor modulators on the market, such as Mayzent®, Zeposia® and Ponvory®, may access at least parts of this CNS mechanism. The study supports B12 supplementation with S1P receptor modulators with the goal of improving drug efficacy for this class of medicines.
The study also opens new avenues on how the B12-TCN2-CD320 pathway is regulated by sphingolipids, specifically sphingosine, a naturally occurring and endogenous structural analog of fingolimod, toward improving future MS therapies, the author said.
“It supports creating brain-targeted B12 formulations. In the future, this mechanism might also extend to novel treatments of other neuroinflammatory and neurodegenerative conditions.”
https://www.cell.com/cell-reports/fulltext/S2211-1247(23)01557-7
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Ffty720-requires-vitamin&filter=22
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