WELCOME TO OUR PARKINSON'S PLACE!

I HAVE PARKINSON'S DISEASES AND THOUGHT IT WOULD BE NICE TO HAVE A PLACE WHERE THE CONTENTS OF UPDATED NEWS IS FOUND IN ONE PLACE. THAT IS WHY I BEGAN THIS BLOG.

I COPY NEWS ARTICLES PERTAINING TO RESEARCH, NEWS AND INFORMATION FOR PARKINSON'S DISEASE, DEMENTIA, THE BRAIN, DEPRESSION AND PARKINSON'S WITH DYSTONIA. I ALSO POST ABOUT FUNDRAISING FOR PARKINSON'S DISEASE AND EVENTS. I TRY TO BE UP-TO-DATE AS POSSIBLE.

I AM NOT RESPONSIBLE FOR IT'S CONTENTS. I AM JUST A COPIER OF INFORMATION SEARCHED ON THE COMPUTER. PLEASE UNDERSTAND THE COPIES ARE JUST THAT, COPIES AND AT TIMES, I AM UNABLE TO ENLARGE THE WORDING OR KEEP IT UNIFORMED AS I WISH. IT IS IMPORTANT TO UNDERSTAND I AM A PERSON WITH PARKINSON'S DISEASE. I HAVE NO MEDICAL EDUCATION,

I JUST WANT TO SHARE WITH YOU WHAT I READ ON THE INTERNET. IT IS UP TO YOU TO DECIDE WHETHER TO READ IT AND TALK IT OVER WITH YOUR DOCTOR. I AM JUST THE COPIER OF DOCUMENTS FROM THE COMPUTER. I DO NOT HAVE PROOF OF FACT OR FICTION OF THE ARTICLE. I ALSO TRY TO PLACE A LINK AT THE BOTTOM OF EACH ARTICLE TO SHOW WHERE I RECEIVED THE INFORMATION SO THAT YOU MAY WANT TO VISIT THEIR SITE.

THIS IS FOR YOU TO READ AND TO ALWAYS KEEP AN OPEN MIND.

PLEASE DISCUSS THIS WITH YOUR DOCTOR, SHOULD YOU HAVE ANY QUESTIONS, OR CONCERNS. NEVER DO ANYTHING WITHOUT TALKING TO YOUR DOCTOR FIRST..

I DO NOT MAKE ANY MONEY FROM THIS WEBSITE. I VOLUNTEER MY TIME TO HELP ALL OF US TO BE INFORMED.

I WILL NOT ACCEPT ANY ADVERTISEMENT OR HEALING POWERS, HEALING FROM HERBS AND ETC. UNLESS IT HAS GONE THROUGH TRIALS AND APPROVED BY FDA. IT WILL GO INTO SPAM.

THIS IS A FREE SITE FOR ALL WITH NO ADVERTISEMENTS

THANK YOU FOR VISITING! TOGETHER WE CAN MAKE A DIFFERENCE!

TRANSLATE

Wednesday, May 29, 2019

New compounds could be used to treat autoimmune disorders

 MAY 29, 2019   by Rockefeller


Newly-developed molecules bind to a key enzyme pocket to inhibit its activity, and possibly prevent autoimmune responses. Credit: Laboratory of RNA Molecular Biology at The Rockefeller University

The immune system is programmed to rid the body of biological bad guys—like viruses and dangerous bacteria—but its precision isn't guaranteed. In the tens of millions of Americans suffering from autoimmune diseases, the system mistakes normal cells for malicious invaders, prompting the body to engage in self-destructive behavior. This diverse class of conditions, which includes Type I diabetes, lupus, and multiple sclerosis, can be very difficult to treat.
In a new report in Nature Communications, researchers in the laboratory of Thomas Tuschl describe their development of small molecules that inhibit one of the main enzymes implicated in misguided immune responses. This research could lead to new treatments for people with certain  and, more broadly, sheds light on the causes of autoimmunity.
Cellular security
In eukaryotes, including humans, DNA typically resides in a cell's nucleus, or in other sequestered organelles such as mitochondria. So if DNA is found outside of these compartments—in the cell's cytosol—the  goes into high alert, assuming the genetic material was leaked by an invading bacterium or virus.
In 2013, researchers discovered an enzyme called cyclic GMP-AMP synthase, or cGAS, that detects and binds to cytosolic DNA to initiate a —a cascade of cellular signaling events that leads to immune activation and usually ends with the destruction of the DNA-shedding pathogen.
Yet, cytosolic DNA isn't always a sign of infection. Sometimes it's produced by the body's own cells—and cGAS does not discriminate between infectious and innocuous DNA. The enzyme will bind to perfectly harmless , prompting an immune response even in the absence of an intruder.
"There is no specificity. So in addition to sensing foreign microbial DNA, cGAS will also sense aberrant cytosolic DNA made by the host," says postdoctoral associate Lodoe Lama. "And this lack of self versus non-self specificity could be driving autoimmune reactions."
Since the discovery of cGAS, researchers in the Tuschl laboratory have sought to understand its potential clinical relevance. If autoimmune disorders are the result of an erroneously activated immune system, then perhaps, they believe, a cGAS inhibitor could be used to treat these conditions.
Newly-developed molecules bind to a key enzyme pocket to inhibit its activity, and possibly prevent autoimmune responses. Credit: Rockefeller University
Until now, no potent and specific small-molecule compound existed to block cGAS in human cells, though the researchers previously identified one that can do the job in mouse cells. Hoping to fill this gap, Tuschl's team collaborated with Rockefeller's High-Throughput and Spectroscopy Resource Center to scan through a library of almost 300,000 small molecules, searching for one that might target human cGAS.
Building a blocker
Through their screen, the researchers identified two molecules that showed some activity against cGAS—but this result was just the beginning of a long process towards developing an inhibitor that might be used in a clinical setting.
"The hits from library compounds were a great starting point, but they were not potent enough," says Lama. "So we used them as molecular scaffolds on which to make improvements, altering their structures in ways that would increase potency and also reduce toxicity."
Working with the Tri-Institutional Therapeutics Discovery Institute, the researchers modified one of their original scaffolds to create three compounds that blocked cGAS activity in human cells—making them the first molecules with this capability. Further analysis by researchers at Memorial Sloan Kettering Cancer Center revealed that the compounds inhibit cGAS by wedging into a pocket of the enzyme that is key to its activation.
The compounds are now being further optimized for potential use in patients, with an initial focus on treatment of the rare genetic disease Aicardi-Goutières syndrome. People with this condition accumulate abnormal cytosolic DNA that activates cGAS, leading to serious neurological problems. A drug that blocks the enzyme would therefore be of tremendous therapeutic value to those with the disease, who currently have few treatment options.
"This class of drug could potentially also be used to treat more common diseases, such as systemic lupus erythematosus, and possibly neurodegenerative diseases that include inflammatory contributions, such as Parkinson's disease," says Tuschl.
Further, the researchers believe that these compounds could serve as practical laboratory tools.
"Scientists will now have simple means by which to inhibit cGAS in human cells," says Lama. "And that could be immensely useful for studying and understanding the mechanisms that lead to autoimmune responses."
More information: Lodoe Lama et al, Development of human cGAS-specific small-molecule inhibitors for repression of dsDNA-triggered interferon expression, Nature Communications (2019).  DOI: 10.1038/s41467-019-08620-4

Journal information: Nature Communications
Provided by Rockefeller University 

https://medicalxpress.com/news/2019-05-compounds-autoimmune-disorders.html

No comments:

Post a Comment