Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms, 2019, Korte and Straub

Andy · Nov 5, 2019

Today, inflammatory rheumatic disorders are effectively treated, but many patients still suffer from residual fatigue. This work presents pathophysiological mechanisms of fatigue. First, cytokines can interfere with neurotransmitter release at the preterminal ending. Second, a long-term increase in serum concentrations of proinflammatory cytokines increase the uptake and breakdown of monoamines (serotonin, noradrenaline and dopamine). Third, chronic inflammation can also decrease monoaminergic neurotransmission via oxidative stress (oxidation of tetrahydrobiopterin [BH4]). Fourth, proinflammatory cytokines increase the level of enzyme indoleamine-2, 3-dioxygenase activity and shunt tryptophan away from the serotonin pathway. Fifth, oxidative stress stimulates astrocytes to inhibit excitatory amino acid transporters. Sixth, astrocytes produce kynurenic acid that acts as an antagonist on the α7-nicotinic acetylcholine receptor to inhibit dopamine release. Jointly, these actions result in increased glutamatergic and decreased monoaminergic neurotransmission. The above-described pathophysiological mechanisms negatively affect brain functioning in areas that are involved in fatigue.
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Open access, https://academic.oup.com/rheumatology/article/58/Supplement_5/v35/5611826

lansbergen · Nov 5, 2019

Sixth, astrocytes produce kynurenic acid that acts as an antagonist on the α7-nicotinic acetylcholine receptor to inhibit dopamine release.

And levamisole is an allosteric a7nAchr modulator

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Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms, 2019, Korte and Straub

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Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms, 2019, Korte and Straub

Andy Committee Member

lansbergen Senior Member (Voting Rights)

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