Anti-prion compounds.

<p>(<b>A</b>) Timeline of the pharmacological experiments in <i>tg</i>a<i>20</i> COCS. Drug treatments were initiated at 21 dpi and re-added with each medium change (arrows). Longitudinal analyses revealed no cell loss at <35 dpi. Prion replication was assessed at 35 dpi, actively ongoing cell death at 39–42 dpi (PI; fodrin; TUNEL) and severe neuronal loss at 42–45 dpi (NeuN). (<b>B</b>) Representative PrP^Sc immunoblots of <i>wt</i> COCS challenged with RML prions (+) or NBH (−) and treated with compounds at 21–35 dpi. Blots were probed with POM1. (<b>C</b>) Total PrP^Sc (all PrP^Sc bands) was quantified densitometrically and compared to untreated RML-infected COCS (grey). Red: compounds which were reported to interact with PrP^C or PrP^Sc. (<b>D</b>) Misfolded protein assay (upper panel) and scrapie cell assay (lower panel) of all <i>wt</i> samples from C. Relative aggregation and infectivity: values were compared to untreated RML-infected COCS ± s.d. (<b>E</b>–<b>F</b>) NeuN morphometry (lower panel) of <i>tg</i>a<i>20</i> slices exposed to RML or NBH and treated with compounds from 21–42 dpi. All compounds reducing aggregation and/or infectivity were neuroprotective except guanabenz. In contrast, E64d was neuroprotective although it enhanced prion infectivity. (<b>F</b>) NeuN staining showing CGL damage by RML infection (middle) and its prevention by pentosan polysulphate (right).