| First Author | Meske V | Year | 2019 |
| Journal | Neuropharmacology | Volume | 151 |
| Pages | 159-170 | PubMed ID | 31004654 |
| Mgi Jnum | J:289724 | Mgi Id | MGI:6434629 |
| Doi | 10.1016/j.neuropharm.2019.04.012 | Citation | Meske V, et al. (2019) NPC1-deficient neurons are selectively vulnerable for statin treatment. Neuropharmacology 151:159-170 |
| abstractText | 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 approximately 95% and approximately 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. |
