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How stopping cell death may help prevent rheumatoid arthritis

admin by admin
July 6, 2019
in Longevity & Anti Aging
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How stopping cell death may help prevent rheumatoid arthritis
Research in mice now shows that a specific cell death mechanism can lead to rheumatoid arthritis. Stopping this mechanism could help prevent this condition from developing, the authors argue.
Researchers uncover a key cellular mechanism involved in RA that has potential therapeutic implications.

Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized mainly by pain and stiffness in the joints due to inflammation in the joint lining.

Some of the main risk factors for RA are age (people over 60 are more at risk), sex (this condition is more common in women), and the expression of specific genes.

According to the Arthritis Foundation, around 54 million adults in the United States have a diagnosis of arthritis. Other data indicate that RA affects approximately 1% of the world’s population.

Although this condition is widespread, scientists know little about what actually causes it. This means that doctors often find it challenging to suggest effective preventive strategies.

Recently, teams from numerous research institutions — including the University of Cologne in Germany, the VIB institute and Ghent University in Belgium, the Biomedical Sciences Research Center “Alexander Fleming” in Athens, Greece, and the University of Tokyo in Japan — have been looking at mouse models of this autoinflammatory condition. They have been studying a key mechanism, which, they think, may help specialists learn to prevent cases of RA.

The teams report — in the journal Nature Cell Biology — the discovery of a cellular mechanism that appears to play a crucial role in the development of the condition in some instances.

The researchers say that targeting this mechanism may help keep RA at bay, at least in a subset of at-risk people.

‘A very important finding’

The new study furthers previous research conducted by scientists from VIB and the University of Ghent, which showed that the protein A20 could prevent inflammation in the joints and stop arthritis.

The investigators explain that poor A20 function has associations with inflammation and inflammatory diseases in mice and humans.

In the current research, the team engineered a set of mice to express A20 with a particular mutation, which led the mice to develop arthritis spontaneously. The researchers say this happens because the mutated protein A20 is unable to prevent the death of macrophages, which are a kind of immune cell.

Macrophages are white blood cells whose primary function is to find and destroy cellular debris, as well as harmful foreign molecules that infiltrate the body. In arthritis, macrophages die in a process that scientists call necroptosis, which heightens the state of inflammation in the system.

In the study, co-author Marietta Armaka notes that the team “revealed how the particular type of macrophage demise shapes the activation of synovial fibroblasts, a key cell type that orchestrates the destruction of cartilage and bone tissue in RA.”

Thus, the researchers point out that stopping necroptosis from occurring can help prevent RA, at least in individuals who are genetically more likely to experience this form of macrophage death.

Through their experiments, co-author Prof. Geert van Loo explains, “[w]e could […] identify why these macrophages are dying and could demonstrate the importance of a specific part in the protein A20 for the prevention of cell death and RA development.”

The authors argue that the study’s findings are significant because they could lead to the development of novel therapies for this autoimmune condition.

“From a therapeutic perspective, this is a very important finding, since it suggests that drugs inhibiting cell death could be effective in the treatment of RA, at least in a subset of patients where macrophage death could provide the underlying trigger.”

Co-author Prof. Manolis Pasparakis

The researchers note that several pharmaceutical companies are currently developing drugs capable of inhibiting this form of cell death. So, there is hope that, in the future, scientists will be able to target this mechanism successfully, extending this therapeutical approach to humans.

Tags: Rheumatoid Arthritis
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