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Tau Protein Accumulation and Inhibition

HSP90 inhibitors induce HSP70 protein levels and reduce total Tau levels, largely in the absence of toxicity.

HSP90 inhibitors induce HSP70 protein levels and reduce total Tau levels, largely in the absence of toxicity. H4 cells were treated with a 1 μM concentration of small molecule HSP90 inhibitors for 48 hours. Cells were treated in triplicate for In-Cell Western (ICW) analysis and validated by Western blot (WB) in separate experiments. Compounds A - J are 10 novel and distinct compounds with putative HSP90-inhibiting activity. Veh indicates cells treated with DMSO only.

Data courtesy of Chad Dickey, Mayo Clinic.

figure1TauProtein

Predominantly non-toxic novel HSP90 inhibitors lower tau protein levels at a tolerable dosage.

Human H4 neuroglioma cells were treated in triplicate for 48 h with 1 of 10 HSP90 inhibitors (1 μM; identified by letter on x-axis). Tau (black bars) and GAPDH (gray bars) protein expression were simultaneously measured by ICW analysis. Expression of tau and GAPDH is presented a percentage of their respective vehicle control levels. Significance was measured for tau levels by comparing GAPDH to tau expression. By student t-test, * indicates p-value < 0.05, ** indicates p-value < 0.01, and *** indicates p-value < 0.001. Toxicity was determined by comparing GAPDH levels in treated cells to vehicle controls cells. † indicates p-value < 0.05.

Data courtesy of Chad Dickey, Mayo Clinic.

fig2TauProtein


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