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Fig. 4 | Acta Neuropathologica Communications

Fig. 4

From: Ischemic axonal injury up-regulates MARK4 in cortical neurons and primes tau phosphorylation and aggregation

Fig. 4

Mark4 potentiates tau phosphorylation in vivo and aggregation in vitro. Immunolabeling for pTau-Ser262 (purple) in stroke-injured FR+ (red) cells with uninjured NeuN+ cortical neurons (green) (upper panels, a). Immunolabeling for Mark4 (green) and 12E8 (white) in FR+ (red) cells (lower panels, a). Subcortical stroke with retrograde tracing highlighting stroke-injured cortical neurons 7d after stroke (left, b). Cortical tissue overlying stroke enriched for stroke-injured FR+ cells is selectively isolated (middle, b). ECLIA for pTau-Thr231 (pg/mL) in ipsilateral cortex of sham and stroke (b) (n = 8/grp, p = 0.012). Schematic of FRET-based tau biosensor assay used to measure tau aggregation in presence of human Mark4 (upper, c). Representative images of FRET signal induced by tau aggregation in presence of varying concentrations of transfected human Mark4 protein (pM) with or without Mark enzymatic inhibitor (left, c). Tau aggregation quantified by integrated FRET density in tau-biosensor cells in presence of 20 nM of tau repeat domains and increasing concentrations of human Mark4 (1–250 pM) and Mark enzymatic inhibition (10 μM) (right, c) (p < 0.0001 by ANOVA) with specific statistical comparison shown with brackets and p-values. Scale bars = 10 μm (a); 500 μm (b). Mean ± S.E.M

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