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Fig. 7 | Molecular Neurodegeneration

Fig. 7

From: Small molecule inhibitors of α-synuclein oligomers identified by targeting early dopamine-mediated motor impairment in C. elegans

Fig. 7

Losartan, rapamycin, and rifabutin reduce α-synuclein oligomers in mammalian neurons. (a) Five positive hits were tested for their ability to reduce α-synuclein oligomer levels in rat primary cortical neurons measured with YFP-based protein-fragment complementation. No statistically significant changes were observed in (b) total α-synuclein levels measured by immunohistochemistry or (c) fluorescence of full-length YFP alone. Fluorescence intensity was analyzed using Imaris image analysis software by measuring the mean fluorescence intensity of α-synuclein positive neurons throughout a 3D field of view generated by z-stack image acquisition using the “surfaces” module. The value generated for each neuron was normalized to the mean fluorescence intensity of neurons treated with vehicle alone (N = 3–4 replicates of n = 10 fields of view for each treatment; each data point represents an individual replicate) (nested one-way ANOVA with Dunnett’s post-hoc test, *p < 0.05, ***p < 0.001). (d) Top & Middle: Representative fluorescent microscopy images of neurons treated with vehicle, losartan, rapamycin, or rifabutin and co-expressing human α-synuclein tagged with the N- or C-terminal half of YFP. Bottom: Representative fluorescent microscopy images of neurons treated with vehicle, losartan, rapamycin, or rifabutin and expressing YFP alone. Scale bars are 10 μM. (e) Representative immunoblot to detect oligomers of split YFP-tagged α-synuclein (crosslinked) in rat primary cortical neuron lysates (actin used as a loading control)

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