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In earlier work, the team had investigated a small molecule that blocks an enzyme called dual-specificity tyrosine-phosphorylationregulated kinase 1A (DYRK1A
The role of DYRK1A
inhibitor on tau phosphorylation.
Wang et al., "[beta]-Carboline compounds, including harmine, inhibit DYRK1A
and tau phosphorylation at multiple Alzheimer's disease-related sites," PLoS One, vol.
Wang et al., "The GBA, DYRK1A
and MS4A6A polymorphisms influence the age at onset of Chinese Parkinson patients," Neuroscience Letters, vol.
This observation was critical in motivating the assessment of L-LTP in Ts65Dn mice here, given that dysfunction of NMDA receptors in DS was originally theoretically predicted as the potential consequence of the inhibition of calcineurin activity due to overexpression of chromosome 21 gene products such as RCAN1 and DYRK1A
(perhaps coupled to elevated amounts of reactive oxidative species) .
EGCG is believed to work by inhibiting the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A
) enzyme, which is overexpressed in people with Down syndrome and which appears to play a role in the pathogenesis of intellectual deficits in these individuals.
Another study revealed that miR-10b promotes cell proliferation, migration, and invasion by inhibiting the expression of the TBX5 transcription factor, which led to repression of the DYRK1A
and PTEN tumor suppressor genes .
Among them, we chose three genes, which are RUNX1, dual-specificity tyrosine-(Y)-phosphoiylation regulated kinase 1A (DYRK1A
), and potassium inwardly-rectifying channel, subfamily J, member 15 (KCNJ15), based on their reported functions.
Another therapeutic topic of interest resides on [beta]-carbolines' action upon DATs, since these alkaloids inhibit DYRK1A
, a kinase found in the striatum which act as an important modulator of dopaminergic transmission and in dopamine vesicles' endocytosis (Brierley and Davidson, 2012).