PCSK9 Affects Astrocyte Cholesterol Metabolism and Reduces Neuron Cholesterol Supplying In Vitro: Potential Implications in Alzheimer's Disease.

ABSTRACT: The Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) involvement in Alzheimer's disease (AD) is poorly investigated. We evaluated the in vitro PCSK9 modulation of astrocyte cholesterol metabolism and neuronal cholesterol supplying, which is fundamental for neuronal functions. Moreover, we investigated PCSK9 neurotoxic effects. In human astrocytoma cells, PCSK9 reduced cholesterol content (-20%; p < 0.05), with a greater effect in presence of beta amyloid peptide (Aβ) (-37%; p < 0.01). PCSK9 increased cholesterol synthesis and reduced the uptake of apoE-HDL-derived cholesterol (-36%; p < 0.0001), as well as the LDL receptor (LDLR) and the apoE receptor 2 (ApoER2) expression (-66% and -31%, respectively; p < 0.01). PCSK9 did not modulate ABCA1- an

SUBMITTER: Papotti B 

PROVIDER: S-EPMC9602670 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature