Strategies for killing two birds with one stone: treating joint pain and cognitive impairment in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease that causes extensive joint inflammation that causes severe pain and discomfort
to patients.
But did you know that the disease is often accompanied by neuropsychiatric complications such as cognitive impairment and depression? Previous studies have shown that up to 70% of people with rheumatoid arthritis may have this cognitive impairment
.
These neurological symptoms are thought to be caused by neuroinflammation, which stems from inflammation
throughout the body.
However, the exact mechanism of such cognitive impairment is unclear
.

Previously, C.
Lee, Director of the Center for Cognitive and Social Studies at the Daejeon Institute for Basic Sciences (IBS), South Korea, The team led by Justin Lee conducted research on the hippocampus of people with dementia to better understand the overall mechanism
of memory impairment.

MAO, including MAO-A and MAO-B, are enzymes that catalyze the oxidation of monoamines and bind to the
mitochondrial outer membranes of cells in several organs, such as the brain and immune system.
More than 30 years ago, previous studies showed that MAO inhibitors could relieve pain and stiffness in patients with RA
.
However, there were no follow-up studies on these results, and even today there is a general lack of further studies related to the role of MAO in RA
.

Recently, LEE's team found that interleukin-1β (IL-1β), one of these inflammatory substances that cause RA, causes abnormal expression
of MAO-B fibrosynovial cells (FLSs) isolated from the joint tissue of RA patients.
The study found that MAO-B and GABA were both abnormally expressed
in these cells.

The team's findings suggest that MAO-B and MAO-B products, such as GABA and H2O2, can worsen joint inflammation
by upregulating the expression of pro-inflammatory factors.

Notably, the researchers also observed that animal models of RA showed an increase
in cognitive impairment.
In conventional behavioral experiments, normally healthy mice have no difficulty
remembering new objects or new locations.
On the other hand, studies have shown that RA model mice are unable to distinguish between new things and objects, which is a hallmark
of cognitive impairment.

Similar to joint tissue, there is an abnormal increase in the secretion of mao-b-dependent GABA in the hippocampus, which is thought to be the main cause
of cognitive dysfunction.
Hippocampal astrocyte mao-b mediated GABA inhibits neurons, leading to memory and cognitive impairment
.
Based on the fact that astrocytes are sensitive to inflammation, it is hypothesized that astrocytes are also affected during the progression of RA disease, leading to cognitive impairment
.

First author Dr WON Woojin said: "So far, research on rheumatoid arthritis has focused only on the mechanisms of inflammation, so the causes and treatments for cognitive impairment are unclear
.

Inhibiting peripheral and central MAO-B ameliorates joint inflammation and cognitive impairment in rheumatoid arthritis