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The Genetic Origins of Multiple Sclerosis in Northern Europeans Revealed by Ancient DNA

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Northern Europeans have a higher risk of multiple sclerosis due to ancient DNA, a study reveals. About 5,000 years ago, people flocked to this area.

This discovery emerged from a large-scale study comparing modern DNA with DNA obtained from ancient human teeth and bones. This allowed scientists to explore prehistoric migration and associated disease-related genes.

Results show that when the Yamnaya people migrated from present-day Ukraine and Russia to northwestern Europe during the Bronze Age, they carried a genetic mutation. This mutation is now known to increase the risk of multiple sclerosis.

The study, published in the journal Nature, suggests that these genes not only allowed the Yamnaya to flourish and spread but also protected them from infectious diseases carried by cattle and sheep.

The project, led by Eske Willerslev and the University of Copenhagen, is pioneering ancient DNA research and comparing it to similar research, including tracking down early cousins such as Neanderthals.

The process of ancient DNA extraction at the Lundbeck Foundation Geogenetics Center in Copenhagen.Michal Schlosser / University of Copenhagen (via AP)

This gene bank’s first exploration of multiple sclerosis is especially relevant since the disease is most common among people of white Scandinavian descent, yet the reason remains unknown.

Scientists believe certain infections can cause MS in genetically susceptible individuals. Over 230 genetic mutations have been identified that may increase the risk of this disease.

The study uncovered major changes in the population of northern Europe, tracing the migration of the Yamnaya people around 5,000 years ago. The gene bank was used to compare ancient DNA with around 400,000 modern humans

Comparisons revealed that MS-related genetic variants remained in the north, the direction the Yamnaya migrated, rather than in southern Europe. This supports the idea that the Yamnaya people are the closest ancestors of modern Danes, and the incidence of MS is particularly high in Scandinavian countries.

Dr. Astrid Iversen from the University of Oxford explains how exposure to animal-based bacteria may lead to imbalances in the immune system, possibly playing a role in the early development of autoimmune diseases.

While the study provides a potential explanation for the North-South MS disparity in Europe, further research is required to confirm the link. This statement comes from New York’s M.D., Samira Asghari, a genetics expert at Sinai School of Medicine, who was not involved in the study.

Source: www.nbcnews.com

Possible Origin of Multiple Sclerosis Gene: Protection Against Infection in Animals

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Multiple sclerosis is an autoimmune disease that occurs when the immune system starts attacking the nerves.

Katerina Conn/Science Photo Library

The largest genetic database of ancient humans to date is shedding new light on why people vary in modern conditions such as multiple sclerosis (MS) and other genetic traits such as height.

One of the findings is that the genes behind MS may have become more common because they helped people resist infections transmitted from animals.

Other findings include why Alzheimer’s disease is more common in some groups than others and why people in northern Europe tend to be taller than people in the southern part of the continent. Includes description.

“What happened thousands of years ago can have a very serious impact on the health and longevity of people living today,” he says. Evan Irving Pease at the University of Copenhagen, Denmark.

The genes of people of European and Western Asian ancestry have been shaped by three major waves of migration. Modern hunter-gatherer humans first arrived in these areas about 45,000 years ago. Then, about 11,000 years ago, a wave of farmers arrived from the Middle East, followed by a further influx of pastoralists, now called the Yamnaya, from the Eurasian steppe.

To understand how these popular movements shaped the modern medical landscape, Irving Pease's team collected bone and tooth samples from approximately 5,000 ancient sites found in museum collections across Europe and Western Asia. The oldest one is 34,000 years old.

The latest study reports on the first batch of samples analyzed based on approximately 1600 individuals. The researchers compared these people to the genetic data of 410,000 people in a huge medical dataset called the UK Biobank, and analyzed only white participants to select participants with European ancestry. did.

The research team started by focusing on MS, an autoimmune disease that occurs when the immune system begins to attack nerves, often leading to progressive disability.What previous research has found 233 genetic variants associated with increased risk of MS.

Among modern people in the UK, those at high genetic risk of multiple sclerosis are more likely to have Yamnaya ancestry, a study has shown. The research team also found that some of these MS-predisposing genetic mutations first arose in the Yamnaya tribe and became more frequent among their descendants as they spread westward through Europe.

Given that some of the 233 variants associated with MS also affect the immune system, and that the Yamnaya people have lived among animals, researchers believe that the genes behind MS are probably The researchers concluded that the species may help protect against bacteria and viruses that can be transmitted to humans. animal.The team has previously shown that Some MS risk variants are associated with partial resistance to tuberculosis.

In another paper, researchers have revealed how our ancestry influences our genetic risk for Alzheimer's disease. Modern humans are more likely to have a gene called . Apo E4If you have more ancestors from Europe's first hunter-gatherers, you have a higher risk of developing Alzheimer's disease.

Another variant of this gene is Apo E2The result is a lower risk of Alzheimer's disease, which likely occurred in the incoming Yamnaya people because it provided protection against malaria and unknown viral infections, the researchers wrote in their paper.

Variants that protect against Alzheimer's disease do not confer a reproductive advantage, so they may not have been selected by evolution to have an effect on dementia, given that dementia typically develops long after people have had children. Yes, researchers say. benjamin trumbull from Arizona State University and was not involved in any research.

“The great thing about this paper is that they go further back in time and say what was advantageous or disadvantageous at that time,” Trumbull said. “Too often we look at our modern environment and say: [a certain gene] Purely harmful. We have to consider what the selection pressures were at different points in time. ”

A further finding from the analysis is that among people living in Europe, those with more Yamnaya ancestry tend to be taller, which explains why Northern Europeans are, on average, taller than Southern Europeans. This may explain why it is so expensive.

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Source: www.newscientist.com

The correlation between vitamin B12 deficiency and multiple sclerosis

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A groundbreaking study focused on astrocytes in the brain has uncovered a new molecular link between vitamin B12 and multiple sclerosis (MS). This study demonstrates that his FDA-approved MS treatment drug, fingolimod, can modulate the B12 transmission pathway, highlighting the potential of B12 supplementation in MS treatment. Credit: SciTechDaily.com

Study results identify molecular signaling pathways that have the potential to enhance current MS treatments.

Scientists have noted interesting similarities between vitamin B deficiency and B vitamins for decades.12 – Essential nutrients that support the healthy development and function of the central nervous system (CNS) – and Multiple Sclerosis (MS) is a chronic disease in which the body’s immune system attacks the CNS, causing neurodegeneration.

Both are vitamin B12 (also known as cobalamin) deficiency and multiple sclerosis cause similar neurological symptoms, including numbness or tingling in the hands and feet, loss of vision, difficulty walking or talking normally, and cognitive impairment such as memory loss .

New research reveals molecular connections

In a new study published online on December 8, 2023, cell reportSanford Burnham Prebys researchers are working with other collaborators to describe a new molecular relationship between B vitamins.12 The other is MS, which occurs in astrocytes, which are important non-neuroglial cells in the brain.

The findings of the study’s senior authors Jerrold Chun, MD, PhD, professor and senior vice president for neuroscience drug discovery, and Yasuyuki Kihara, PhD, associate research professor and co-corresponding author, and their colleagues, open new ways to conduct research. It suggests. Improving MS treatment through CNS-B12 Replenishment.

“Covalent molecular bonds of vitamin B in the brain”12 A carrier protein known as transcobalamin 2 or TCN2 and the FDA-approved MS drug fingolimod provide a mechanistic link between B and B.12 “Signal transduction and MS lead to reduced neuroinflammation and possibly neurodegeneration,” Chun said.

“Strengthen Brain B”12 When used in combination with fingolimod or potentially related molecules, it could potentially enhance both current and future MS treatments. ”

Study details and impact

In their paper, the Sanford Burnham Prebys team, along with collaborators from the University of Southern California, Japan’s Juntendo University, Tokyo University of Pharmacy, and the State University of New York, focused on the molecular function of FTY720, or fingolimod (Gilenya®). . ), a sphingosine 1-phosphate (S1P) receptor modulator that suppresses the distribution of T and B immune cells that mistakenly attack the brains of MS patients.

Using animal models of MS and postmortem human brains, researchers found that fingolimod suppresses neuroinflammation by functionally and physically modulating group B.12 Enhance communication channels, especially B12 A receptor called CD320 must take up and use the necessary B12 If bound to TCN2 distributing B12 throughout the body, including the CNS. This known process was newly identified through interaction with fingolimod within astrocytes. Importantly, this relationship was also observed in human MS brains.

Of particular note, the researchers reported lower levels of CD320 or dietary B;12 The restriction worsened the disease course and reduced the therapeutic efficacy of fingolimod in animal models of MS.This occurred through a hitchhiking mechanism in which fingolimod binds to TCN2-B.12 This complex allows delivery to all astrocytes via interaction with CD320, and loss of the component disrupts the process and exacerbates the disease.

These new findings further support the use of B .12 It turns out that supplements, particularly fingolimod, can correct astrocyte B disorders in terms of delivering vitamins to astrocytes in the brain.12 Pathways for MS patients.

Scientists say other commercially available S1P receptor modulators, such as Mayzent®, Zeposia® and Ponvory®, may be able to access at least part of this CNS mechanism.This study supports B12 Supplementation with S1P receptor modulators aimed at improving the efficacy of this class of drugs.

This study also opens new avenues for how B functions.12The -TCN2-CD320 pathway is regulated by sphingolipids, specifically sphingosine, an endogenous structural analog of naturally occurring fingolimod, for future improvements in MS treatment, Chun said.

“We support the creation of B that targets the brain.”12 formulation. In the future, this mechanism may be extended to new treatments for other neuroinflammatory and neurodegenerative diseases. ”

Reference: “FTY720 requires astrocyte vitamin B12-TCN2-CD320 signaling to reduce disease in animal models of multiple sclerosis” (Deepa Jonnalagadda, Yasuyuki Kihara, Aran Groves, Manisha Ray, Arjun Saha, Clayton Ellington, Hyeon-Cheol Lee-Okada), Tomomi Furuhata, Takehiko Yokomizo, Edward V. Quadros, Richard Rivera, Jerrold Chun, December 7, 2023. cell report.
DOI: 10.1016/j.celrep.2023.113545

Additional authors of the study include Sanford Burnham Prebys, Alan Groves, Sanford Burnham Prebys, Deepa Johnnalagadda, Manisha Ray, Clayton Ellington, and Richard Rivera of the University of California, San Diego . Arjun Saha, University of Southern California. Juntendo University, Hyeon-Cheol Lee-Okada and Takehiko Yokomizo. Tomomi Furuhata (Tokyo University of Pharmacy) Edward V. Quadros, Downtown Medical Center, New York.

This research was supported by a grant from the National Institute of Neurological Disorders and Stroke. National Institutes of Health (R01NS103940), Novartis, Ministry of Education, Culture, Sports, Science and Technology/JSPS KAKENHI (18H02627, 19KK0199, 21H04798, 18K16246 and 21K08565). Additional support was provided by the Uehara Memorial Foundation, Kanae Medical Foundation, Mochida Memorial Medical and Pharmaceutical Research Foundation, Human Frontier Science Program, and the University of California, San Diego Medical Scientist Training Program and Pharmacology Training Grant (T32GM007752). . ).

Source: scitechdaily.com