Broad kinase inhibition mitigates early neuronal dysfunction in tauopathy
We treated early stage tau transgenic mice with a multi-target kinase inhibitor. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging technique called manganese-enhanced magnetic resonance imaging (MEMRI) with quantitative R1 mapping. Surprisingly, these benefits occurred despite unchanged hyperphosphorylated tau levels. We identified a cluster of […]
New evidence for P-gp-mediated export of Amyloid-beta peptides in molecular, blood-brain barrier and neuronal models
We present molecular data to demonstrate that both Aβ40 and Aβ42 peptide isoforms directly interact with and are substrates of P-gp. This was reinforced ex vivo by the inhibition of Aβ42 transport in brain capillaries from P-gp-knockout mice. Moreover, we explored whether P-gp could exert the same role in neurons. Comparison between non-neuronal CHO-APP and […]