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Researchers find immune component to rare neurodegenerative disease – California News Times

Immunofluorescent staining of the cerebellum of Npc1-deficient mice with red Purkinje neurons, green activated microglia, and blue nuclei. Massive microglial infiltration and loss of Purkinje neurons cause severe neurological disease in Niemann-Pick disease type C. Credit: Ting-Ting Chu

Researchers at UT Southwest have identified an immune protein associated with a rare neurodegenerative condition known as Niemann-Pick disease type C. This discovery was made in a mouse model and is published online. NatureMay provide a powerful new therapeutic target for Niemann-Pick disease type C, which was identified over a century ago but still lacks effective treatments.

“Niemann-Pick disease has never been considered an immune disorder,” said Dr. Nanyang, an associate professor of immunology and microbiology and research leader. “These discoveries have turned it into a whole new light.”

Niemann-Pick disease type C, which affects about 1 in 150,000 people worldwide, has long been considered a disease of cholesterol metabolism and distribution. This is a well-studied topic in UT Southwestern. MD was awarded the Nobel Prize in 1985 for the discovery of the low-density lipoprotein (LDL) receptor that led to the development of statins.

When the Npc1 gene is mutated, cholesterol is no longer delivered to where it is needed in the cell, and the motor and intellectual abilities that characterize Niemann-Pick disease gradually decline. Yang’s lab, which is not studying cholesterol metabolism, accidentally discovered it while studying an immune protein known as STING, which stands for stimulator of the interferon gene.

STING is an important part of the body’s defense against the virus, usually relying on another protein known as cyclic GMP-AMP synthase (cGAS) to sense DNA and turn on immune genes in the virus. Repel intruders. The cGAS enzyme was identified in UT Southwestern.

STING is a lysosome that travels to organelles to perform various tasks and then acts as a dumping ground for cells. Disposal of STING is important for a proper immune response, Yan explains.According to the research of his laboratory and other researchers, if STING is not properly discarded, STING will continue to signal. Immune cells, Leads to various autoimmune conditions.

Yan et al. Used a technique called proximity labeling to identify proteins that interact with STING as they move intracellularly. This causes other proteins around the protein of interest to glow. After analyzing their data, Yan’s team was surprised to discover that STING is located on the surface of lysosomes and interacts with the protein produced by the Npc1 gene.

Since STING has never been involved in Niemann-Pick disease type C, Yan and his team investigated whether STING could play a role. Researchers have deleted the STING gene from mice that also had the Npc1 gene deleted. Deletion of Npc1 usually causes progressive problems in motor function, but animals with both the Npc1 and Sting genes removed remained healthy.

Further studies suggest that the protein produced by Npc1 has a STING binding site that allows it to enter the lysosome for disposal.when protein What is produced by Npc1 is missing and STING remains intracellularly to propagate Niemann-Pick disease type C. Analysis of cells from patients with human Niemann-Pick disease type C by Yan and his colleagues revealed several immune stimuli. gene It was overactive, as would be expected if there was a flaw in the disposal of STING.

In addition, Yan found that STING signaling was activated independently of cGAS in Niemann-Pick disease. This extends STING’s biology beyond its traditional role in host defense against infection.

Yang says his lab and other labs are investigating the use of experimental drugs that block STING to treat a variety of autoimmune conditions. These compounds may also be useful for Niemann-Pick disease type C.

“If we can demonstrate that these compounds are effective in our animal models, we may be able to provide effective treatments for Niemann-Pick disease. disease patient. ”


Gene therapy is promising for the treatment of Niemann-Pick disease type C1


For more information:
Ting-Ting Chu et al, STING Signaling tonic prime boost mediates Niemann-Pick disease type C. Nature (2021). DOI: 10.1038 / s41586-021-03762-2

Provided by
UT Southwestern Medical Center

Quote: Researchers found a rare neurodegenerative disease (7 2021) obtained on July 21, 2021 from https: //medicalxpress.com/news/2021-07-immune-component-rare-neurodegenerative-disease.html. I found an immune component against (21st of March)

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