NPC1-deficient neurons are selectively vulnerable for statin treatment.
NPC1-deficient neurons are selectively vulnerable for statin treatment.
Neuropharmacology. 2019 Apr 17;:
Authors: Meske V, Albert F, Gerstenberg S, Kallwellis K, Ohm TG
Abstract
Niemann Pick C (NPC) is a fatal hereditary neurovisceral disorder associated with a progressive loss of neurons of unknown mechanism. The disease is caused by mutation in either of two genes, termed npc1 and npc2, accounting for ∼95% and ∼5% of patients, respectively. Recent data suggest a cell-autonomous cause for neuronal cell death. In a former study we could demonstrate that cultured NPC1-deficient (NPC1-/-) neurons are more susceptible to autophagic stress than NPC1-wildtype (wt) neurons. In the present study we tested other stressors for a selective effect on the survival of NPC1-/- neurons. To that end we challenged cultured primary cortical neurons from a NPC mouse model and from wild type littermate mice by a variety of different stressors: glutamate, hydrogen superoxide, osmotic shock and inhibition of HMG-CoA reductase. In all paradigms neurons behave virtually identical with one exception: NPC1 deficient neurons are more vulnerable against a challenge with lovastatin. The analysis of the molecular background provides evidence that statin endangers survival of neurons by interfering in the autophagy of cells.
PMID: 31004654 [PubMed - as supplied by publisher]
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Meske V, Albert F, Gerstenberg S, Kallwellis K, Ohm TG Tags: Neuropharmacology Source Type: research
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