Antiinflammatorische Wirkung von DA-CH5 auf Mikroglia


Till now there is no curative treatment for Parkinson disease (PD) and research in ongoing. In a recent clinical trial, the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4, a drug used to treat Diabetes mellitus type II, has shown good protective effects in PD patients.

New studies with novel dual GLP-1/GIP receptor agonist have shown disease modifying perfomances in the MPTP mouse modell of PD.  Out of the tested analoga DA-CH5 performed best.

As microglia mediated neuroinflammation plays an important role in neurodegenerative diseases like PD, we investigated the effect of DA-CH5 on activated microglia in vitro.




Lipopolysaccharid (LPS)-stimulated microglia were used to mimic brain inflammation in vitro.

Therefore primary rat microglia were activated with 5 ng/ml LPS in the presence or abscence of 10 and 1000 nM DA-CH5.

The effects of DA-CH5 on the mRNA-expression of iNOS, MMP-3, MMP-9, TNF-⍺ and IL-6 were analyzed using quantitative realtime PCR (qPCR). Additionally protein levels of TNF-⍺  were measured using enzyme-linked immunosorbent assay (ELISA).




DA-CH5 showed significant reduction of Cytokine mRNA-expression in iNOS, MMP-3, MMP-9, TNF-⍺ and IL-6. Furthermore DA-CH5 treatment resulted in reduced proteinlevels of TNF-⍺ after 6 and 24h.



DA-CH5 didn`t show any increasing effect on cytokine mRNA and cytokine expression compared to the control group but was able to reduce the expression of proinflammatory cytokine mRNA and cytokines in activated microglia.

Considering recent findings DA-CH5 might be a potential drug to treat PD and other neurodegenerative disease.



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