Die Bedeutung axonaler Pathologie für das Konzept der Neurodegeneration bei der Multiplen Sklerose

Zusammenfassung

Die Effektormechanismen der Multiplen Sklerose (MS) bleiben trotz großer Forschungsanstrengungen unverstanden. Das vorherrschende pathologische Verständnis beinhaltet das hierarchische Aufeinanderfolgen der Trias Inflammation, Demyelinisierung und Axonschaden. Doch neue Untersuchungen haben ergeben, dass axonale Degeneration auch unabhängig von Inflammation und Demyelinisierung auftreten kann. Ziel dieses Artikels ist die kritische Reevaluation des traditionellen Paradigmas der MS-Pathologie. Nicht nur sollen mögliche zelluläre, humorale und metabolische Mechanismen der Axonpathologie beleuchtet, sondern auch das isolierte Auftreten axonaler Schädigung kritisch diskutiert werden. Ein umfassendes Verständnis der pathogenetischen Mechanismen wird zur Verbesserung der Therapiemöglichkeiten bei MS beitragen. Diese sollten nicht mehr nur auf die inflammatorische, sondern auch auf die neurodegenerative Komponente der Erkrankung abzielen.

Abstract

In spite of tremendous scientific effort, the mechanisms underlying multiple sclerosis (MS) still remain to be elucidated. The prevalent pathogenetic concept adheres to the assumption of a strict hierarchical sequence of the triad inflammation, demyelination and axonal damage. However, recent studies have provided evidence that axonal pathology can occur independently of inflammation and demyelination. The present article critically re-evaluates the traditional paradigm of MS pathology. Potential cellular, humoral and metabolic mechanisms of axonal pathology are delineated and the development of isolated axonal damage is assessed. A better understanding of the pathological processes underlying MS is likely to result in an improvement of current therapeutic strategies. These should not only target the inflammatory, but also the neurodegenerative component of the disease.

Schlüsselwörter

Axonschaden - Demyelinisierung - EAE - Inflammation - MS

Keywords

axonal damage - demyelination - EAE - inflammation - MS

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