Method Profile
Patient-derived cortical neurons support separate measurements of cholesterol accumulation, apoptotic staining and NPC1 protein response to JQ1.
Mechanistic comparison of candidate interventions in an NPC1-associated human neuronal phenotype.
iPSC-derived cortical neurons from one patient homozygous for NPC1 I1061T, compared with healthy-control neurons.
Day-30 neurons exposed to JQ1 at 0.3, 1 or 3 μM for up to 72 hours, with untreated and vehicle controls.
Cell systems
Patient and control cortical neurons expressing TUJ1/TBR1.
Measurements
Filipin fluorescence, TUNEL-positive cell proportion, NPC1 immunoblotting and morphological inspection.
Analyze each endpoint against its matched control and preserve the distinct concentration and time comparisons.
Compare patient and control baseline phenotypes, then assess JQ1 concentration and time responses.
One patient genetic background; selected imaging/protein assays report n = 3 repeats, not three donors.
Healthy-control neurons, untreated cultures and DMSO vehicle conditions.
JQ1 reduced filipin and TUNEL-associated measurements and increased NPC1 protein, with the largest responses generally at 72 hours.
A preprint uses cortical neurons from one patient carrying the NPC1 I1061T variant to examine BET inhibition. JQ1 reduced cholesterol staining and apoptotic-cell measurements while increasing NPC1 protein abundance.
