Zusammenfassung
Statine (HMG-CoA-Reduktase-Hemmer) senken signifikant das Schlaganfallrisiko und haben möglicherweise auch therapeutisches Potenzial bei so unterschiedlichen neurologischen Erkrankungen wie der Multiplen Sklerose oder der Demenz vom Alzheimer-Typ. Zusätzlich zur Senkung des Cholesterinspiegels haben Statine davon unabhängige, sog. pleiotrope Wirkungen. Während periphere endotheliale, antithrombotische, antiinflammatorische sowie immunmodulatorische Effekte der Statine gut untersucht sind, ist über mögliche direkte Wirkungen auf Nervenzellen wenig bekannt. Diese Frage ist jedoch durchaus klinisch relevant, weil einige Statine in der Lage sind, die Blut-Hirn-Schranke (BHS) zu überwinden. Neuere experimentelle Studien zeigen erstmals, dass durch Statine die Funktion neuronaler Glutamatrezeptoren inhibiert wird und Neurone vor exzitotoxischen Insulten geschützt werden. Andererseits vermitteln Statine in höherer Dosierung eine Hemmung von Neuritenaussprossung und können sogar neuronale Apoptose induzieren.
Summary
Statins, i.e. HMG-CoA reductase inhibitors, reduce the risk of stroke and may have therapeutic potential for other neurologic diseases, including multiple sclerosis and Alzheimer’s disease. In addition to lowering cholesterol levels, statins exert a number of cholesterol-independent (pleiotropic) effects. While endothelial, anti-thrombotic, anti-inflammatory, and immunomodulatory, i.e. peripheral, effects of statins are well known, little is known about the direct effects on neurons. This may be of clinical relevance because some statins are able to cross the blood-brain barrier. Recent experimental studies demonstrate that statins reduce the activity of neuronal glutamate receptors and protect neurons from excitotoxic insults. At higher doses, however, statins may also inhibit neurite sprouting and even induce neuronal apoptosis.
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Danksagung
Die Autoren bedanken sich bei Joachim Schulz und Christoph Harms für die Zusammenarbeit in Projekten, aus denen Material für diesen Artikel entnommen wurde.
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Der korrespondierende Autor weist auf eine Verbindung mit folgender Firma hin: AstraZeneca
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Bösel, J., Endres, M. Direkte neuronale Effekte von Statinen. Nervenarzt 77, 289–293 (2006). https://doi.org/10.1007/s00115-005-1963-0
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DOI: https://doi.org/10.1007/s00115-005-1963-0