Background

Excitotoxicity, a common hallmark of different neuro-logical disorders including Alzheimer’s disease (AD), is the consequence of exacerbated neuronal stimulation and leads to a high influx of calcium trough membrane gluta-mate receptors [1]. On the other hand, high levels of the cholesterol meta-bolite 24S-hydroxycholesterol (24-HC) have been found in cerebral spinal fluid (CSF) from AD patients [2,3]. Brain cholesterol homeostasis is an essential, tightly-regulated process that ensures neuronal integrity, viability, and func-tion. One of the mechanisms that neurons put to work to regulate the amount of cellular cholesterol is its con-version into the metabolite 24-HC by the 24-cholesterol hydroxylase CYP46A1 [4]. In this work, we explored the possibility that excitotoxicity, a common process tha