Molecular switch for repairing central nervous system disorders

Neurons illustration (stock image).

A molecular switch has the ability to turn on a substance in animals that repairs neurological damage in disorders such as multiple sclerosis (MS), Mayo Clinic researchers discovered. The early research in animal models could advance an already approved Food and Drug Administration therapy and also could lead to new strategies for treating diseases of the central nervous system.

Research by Isobel Scarisbrick, Ph.D., published in the Journal of Neuroscience finds that by genetically switching off a receptor activated by blood proteins, named Protease Activated Receptor 1 (PAR1), the body switches on regeneration of myelin, a fatty substance that coats and protects nerves.

"Myelin regeneration holds tremendous potential to improve function. We showed when we block the PAR1 receptor, neurological healing is much better and happens more quickly. In many cases, the nervous system does have a good capacity for innate repair," says Dr. Scarisbrick, principal investigator and senior author. "This sets the stage for development of new clinically relevant myelin regeneration strategies."

Myelin, Thrombin and the Nervous System

Myelin acts like a wire insulator that protects electrical signals sent through the nervous system. Demyelination, or injury to the myelin, slows electrical signals between brain cells, resulting in loss of sensory and motor function. Sometimes the damage is permanent. Demyelination is found in disorders such as MS, Alzheimer's disease, Huntington's disease, schizophrenia and spinal cord injury.

Thrombin is a protein in blood that aids in healing. However, too much thrombin triggers the PAR1 receptor found on the surface of cells, and this blocks myelin production. Oligodendrocyte progenitor cells capable of myelin regeneration are often found at sites of myelin injury, including demyelinating injuries in multiple sclerosis.

"These oligodendroglia fail to differentiate into mature myelin regenerating cells for reasons that remain poorly understood," says Dr. Scarisbrick. "Our research identifies PAR1 as a molecular switch of myelin regeneration. In this study, we demonstrate that blocking the function of the PAR1, also referred to as the thrombin receptor, promotes myelin regeneration in two unique experimental models of demyelinating disease."

The Research

The research focused on two mouse models. One was an acute model of myelin injury and the other studied chronic demyelination, each modeling unique features of myelin loss present in MS, Alzheimer's disease and other neurological disorders. Researchers genetically blocked PAR1 to block the action of excess thrombin.

The research not only discovered a new molecular switch that turns on myelin regeneration, but also discovered a new interaction between the PAR1 receptor and a very powerful growth system called brain derived neurotropic factor (BDNF). BDNF is like a fertilizer for brain cells that keeps them healthy, functioning and growing.

Significantly, the researchers found that a current Food and Drug Administration-approved drug that inhibits the PAR1 receptor also showed ability to improve myelin production in cells tested in the laboratory.

"It is important to say that we have not and are not advocating that patients take this inhibitor at this time," says Dr. Scarisbrick. "We have not used the drug in animals yet, and it is not ready to put in patients for the purpose of myelin repair. Using cell culture systems, we are showing that this has the potential to improve myelin regeneration."

Additional research is needed to verify and advance the findings toward clinical practice.

The study was made possible by a grant from the National Multiple Sclerosis Society with support from the Mayo Clinic Rehabilitation Medicine Research Center, the Center for Multiple Sclerosis and Autoimmune Neurology and the Mayo Clinic Center for Regenerative Medicine.

---

Story Source:

Materials provided by Mayo Clinic. Original written by Susan Buckles. Note: Content may be edited for style and length.

Molecular switch for repairing central nervous system disorders

Neurons illustration (stock image).

A molecular switch has the ability to turn on a substance in animals that repairs neurological damage in disorders such as multiple sclerosis (MS), Mayo Clinic researchers discovered. The early research in animal models could advance an already approved Food and Drug Administration therapy and also could lead to new strategies for treating diseases of the central nervous system.

Research by Isobel Scarisbrick, Ph.D., published in the Journal of Neuroscience finds that by genetically switching off a receptor activated by blood proteins, named Protease Activated Receptor 1 (PAR1), the body switches on regeneration of myelin, a fatty substance that coats and protects nerves.

"Myelin regeneration holds tremendous potential to improve function. We showed when we block the PAR1 receptor, neurological healing is much better and happens more quickly. In many cases, the nervous system does have a good capacity for innate repair," says Dr. Scarisbrick, principal investigator and senior author. "This sets the stage for development of new clinically relevant myelin regeneration strategies."

Myelin, Thrombin and the Nervous System

Myelin acts like a wire insulator that protects electrical signals sent through the nervous system. Demyelination, or injury to the myelin, slows electrical signals between brain cells, resulting in loss of sensory and motor function. Sometimes the damage is permanent. Demyelination is found in disorders such as MS, Alzheimer's disease, Huntington's disease, schizophrenia and spinal cord injury.

Thrombin is a protein in blood that aids in healing. However, too much thrombin triggers the PAR1 receptor found on the surface of cells, and this blocks myelin production. Oligodendrocyte progenitor cells capable of myelin regeneration are often found at sites of myelin injury, including demyelinating injuries in multiple sclerosis.

"These oligodendroglia fail to differentiate into mature myelin regenerating cells for reasons that remain poorly understood," says Dr. Scarisbrick. "Our research identifies PAR1 as a molecular switch of myelin regeneration. In this study, we demonstrate that blocking the function of the PAR1, also referred to as the thrombin receptor, promotes myelin regeneration in two unique experimental models of demyelinating disease."

The Research

The research focused on two mouse models. One was an acute model of myelin injury and the other studied chronic demyelination, each modeling unique features of myelin loss present in MS, Alzheimer's disease and other neurological disorders. Researchers genetically blocked PAR1 to block the action of excess thrombin.

The research not only discovered a new molecular switch that turns on myelin regeneration, but also discovered a new interaction between the PAR1 receptor and a very powerful growth system called brain derived neurotropic factor (BDNF). BDNF is like a fertilizer for brain cells that keeps them healthy, functioning and growing.

Significantly, the researchers found that a current Food and Drug Administration-approved drug that inhibits the PAR1 receptor also showed ability to improve myelin production in cells tested in the laboratory.

"It is important to say that we have not and are not advocating that patients take this inhibitor at this time," says Dr. Scarisbrick. "We have not used the drug in animals yet, and it is not ready to put in patients for the purpose of myelin repair. Using cell culture systems, we are showing that this has the potential to improve myelin regeneration."

Additional research is needed to verify and advance the findings toward clinical practice.

The study was made possible by a grant from the National Multiple Sclerosis Society with support from the Mayo Clinic Rehabilitation Medicine Research Center, the Center for Multiple Sclerosis and Autoimmune Neurology and the Mayo Clinic Center for Regenerative Medicine.

---

Story Source:

Materials provided by Mayo Clinic. Original written by Susan Buckles. Note: Content may be edited for style and length.

First identified comet to visit our solar system from another star

Comet 2I/Borisov is only the second interstellar object known to have passed through the solar system. These two images, taken by NASA's Hubble Space Telescope, capture the comet appearing near a background galaxy (left) and soon after its closest approach to the Sun (right).

Credit: NASA, ESA, and D. Jewitt (UCLA)

When astronomers see something in the universe that at first glance seems like one-of-a-kind, it's bound to stir up a lot of excitement and attention. Enter comet 2I/Borisov. This mysterious visitor from the depths of space is the first identified comet to arrive here from another star. We don't know from where or when the comet started heading toward our Sun, but it won't hang around for long. The Sun's gravity is slightly deflecting its trajectory, but can't capture it because of the shape of its orbit and high velocity of about 100,000 miles per hour.

Telescopes around the world have been watching the fleeting visitor. NASA's Hubble Space Telescope has provided the sharpest views as the comet skirts by our Sun. Since October the space telescope has been following the comet like a sports photographer following horses speeding around a racetrack. Hubble revealed that the heart of the comet, a loose agglomeration of ices and dust particles, is likely no more than about 3,200 feet across, about the length of nine football fields. Though comet Borisov is the first of its kind, no doubt there are many other comet vagabonds out there, plying the space between stars. Astronomers will eagerly be on the lookout for the next mysterious visitor from far beyond.

These two images, taken by Hubble, capture comet 2I/Borisov streaking though our solar system and on its way back to interstellar space. It is only the second interstellar object known to have passed through the solar system.

Nov. 16, 2019, photo

The comet appears in front of a distant background spiral galaxy (2MASX J10500165-0152029). The galaxy's bright central core is smeared in the image because Hubble was tracking the comet. Comet Borisov was approximately 203 million miles from Earth in this exposure. Its tail of ejected dust streaks off to the upper right. The comet has been artificially colored blue to discriminate fine detail in the halo of dust, or coma, surrounding the central nucleus. It also helps to visually separate the comet from the background galaxy.

Dec. 9, 2019, photo

Hubble revisited the comet shortly after its closest approach to the Sun where it received maximum heating after spending most of its life in frigid interstellar space. The comet also reached a breathtaking maximum speed of about 100,000 miles per hour. Comet Borisov is 185 million miles from Earth in this photo, near the inner edge of the asteroid belt but below it. The nucleus, an agglomeration of ices and dust, is still too small to be resolved. The bright central portion is a coma made up of dust leaving the surface. The comet will make its closest approach to Earth in late December at a distance of 180 million miles.

"Hubble gives us the best upper limit of the size of comet Borisov's nucleus, which is the really important part of the comet," said David Jewitt, a UCLA professor of planetary science and astronomy, whose team has captured the best and sharpest look at this first confirmed interstellar comet. "Surprisingly, our Hubble images show that its nucleus is more than 15 times smaller than earlier investigations suggested it might be. Our Hubble images show that the radius is smaller than half a kilometer. Knowing the size is potentially useful for beginning to estimate how common such objects may be in the solar system and our galaxy. Borisov is the first known interstellar comet, and we would like to learn how many others there are."

Crimean amateur astronomer Gennady Borisov discovered the comet on Aug. 30, 2019, and reported the position measurements to the International Astronomical Union's Minor Planet Center in Cambridge, Massachusetts. The Center for Near-Earth Object Studies at NASA's Jet Propulsion Laboratory in Pasadena, California, working with the Minor Planet Center, computed an orbit for the comet, which shows that it came from elsewhere in our Milky Way galaxy, point of origin unknown.

Nevertheless, observations by numerous telescopes show that the comet's chemical composition is similar to the comets found inside our solar system, providing evidence that comets also form around other stars. By the middle of 2020 the comet will have already zoomed past Jupiter's distance of 500 million miles on its way back into the frozen abyss of interstellar space.

---

Story Source:

Materials provided by NASA/Goddard Space Flight Center. Note: Content may be edited for style and length.

First identified comet to visit our solar system from another star

Comet 2I/Borisov is only the second interstellar object known to have passed through the solar system. These two images, taken by NASA's Hubble Space Telescope, capture the comet appearing near a background galaxy (left) and soon after its closest approach to the Sun (right).

When astronomers see something in the universe that at first glance seems like one-of-a-kind, it's bound to stir up a lot of excitement and attention. Enter comet 2I/Borisov. This mysterious visitor from the depths of space is the first identified comet to arrive here from another star. We don't know from where or when the comet started heading toward our Sun, but it won't hang around for long. The Sun's gravity is slightly deflecting its trajectory, but can't capture it because of the shape of its orbit and high velocity of about 100,000 miles per hour.

Telescopes around the world have been watching the fleeting visitor. NASA's Hubble Space Telescope has provided the sharpest views as the comet skirts by our Sun. Since October the space telescope has been following the comet like a sports photographer following horses speeding around a racetrack. Hubble revealed that the heart of the comet, a loose agglomeration of ices and dust particles, is likely no more than about 3,200 feet across, about the length of nine football fields. Though comet Borisov is the first of its kind, no doubt there are many other comet vagabonds out there, plying the space between stars. Astronomers will eagerly be on the lookout for the next mysterious visitor from far beyond.

These two images, taken by Hubble, capture comet 2I/Borisov streaking though our solar system and on its way back to interstellar space. It is only the second interstellar object known to have passed through the solar system.

Nov. 16, 2019, photo

The comet appears in front of a distant background spiral galaxy (2MASX J10500165-0152029). The galaxy's bright central core is smeared in the image because Hubble was tracking the comet. Comet Borisov was approximately 203 million miles from Earth in this exposure. Its tail of ejected dust streaks off to the upper right. The comet has been artificially colored blue to discriminate fine detail in the halo of dust, or coma, surrounding the central nucleus. It also helps to visually separate the comet from the background galaxy.

Dec. 9, 2019, photo

Hubble revisited the comet shortly after its closest approach to the Sun where it received maximum heating after spending most of its life in frigid interstellar space. The comet also reached a breathtaking maximum speed of about 100,000 miles per hour. Comet Borisov is 185 million miles from Earth in this photo, near the inner edge of the asteroid belt but below it. The nucleus, an agglomeration of ices and dust, is still too small to be resolved. The bright central portion is a coma made up of dust leaving the surface. The comet will make its closest approach to Earth in late December at a distance of 180 million miles.

"Hubble gives us the best upper limit of the size of comet Borisov's nucleus, which is the really important part of the comet," said David Jewitt, a UCLA professor of planetary science and astronomy, whose team has captured the best and sharpest look at this first confirmed interstellar comet. "Surprisingly, our Hubble images show that its nucleus is more than 15 times smaller than earlier investigations suggested it might be. Our Hubble images show that the radius is smaller than half a kilometer. Knowing the size is potentially useful for beginning to estimate how common such objects may be in the solar system and our galaxy. Borisov is the first known interstellar comet, and we would like to learn how many others there are."

Crimean amateur astronomer Gennady Borisov discovered the comet on Aug. 30, 2019, and reported the position measurements to the International Astronomical Union's Minor Planet Center in Cambridge, Massachusetts. The Center for Near-Earth Object Studies at NASA's Jet Propulsion Laboratory in Pasadena, California, working with the Minor Planet Center, computed an orbit for the comet, which shows that it came from elsewhere in our Milky Way galaxy, point of origin unknown.

Nevertheless, observations by numerous telescopes show that the comet's chemical composition is similar to the comets found inside our solar system, providing evidence that comets also form around other stars. By the middle of 2020 the comet will have already zoomed past Jupiter's distance of 500 million miles on its way back into the frozen abyss of interstellar space.

---

Story Source:

Materials provided by NASA/Goddard Space Flight Center. Note: Content may be edited for style and length.