Mikroglia im Kontext der Multiplen Sklerose

 

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Zusammenfassung

Gegenstand und Ziel

Mikroglia sind die residenten Makrophagen des zentralen Nervensystems (ZNS). Sie haben einen wichtigen Anteil an der Aufrechterhaltung von Abwehrmechanismen des ZNS wie der Phagozytose von apoptotischen Zellen und Zelldetritus. Es gibt wachsende Evidenz, die Mikroglia einen Einfluss für die Pathogenese der Multiplen Sklerose (MS) zuschreibt, vor allem in den progredienten Phasen der Erkrankung. Der Einfluss von Mikroglia auf die Pathogenese der MS soll in diesem Übersichtsartikel beleuchtet werden.

Material und Methoden

Es wurde eine PubMed Datenbankanalyse durchgeführt und relevante Artikel bezüglich der Thematik berücksichtigt.

Ergebnisse

MS ist gekennzeichnet durch eine Schädigung der Myelinscheide mit konsekutiver Demyelinisierung und auch axonalem Schaden. Dies wird durch inflammatorische Vorgänge mit Beteiligung von Mikroglia durch Freisetzung tion, Glia reaktiver Sauerstoff- und Stickstoffmetabolite und proinflammatorischer Zytokine wie IL-1beta und TNF-alpha vermittelt. Mikroglia können unterschiedliche Aktivierungszustände einnehmen; den klassischen Aktivierungszustand mit einem inflammatorischen Zytokinmuster (M1) sowie den alternativen Aktivierungszustand (M2), in welchem ein neuroprotektives Zytokinmuster dominiert. Mittlerweile gibt es therapeutische Ansätze, die auf eine mikrogliale Modulation abzielen, z. B. der Nrf2-Signalweg, der durch Dimethylfumarat beeinflusst wird oder die Verringerung von reaktiven Sauerstoffmetaboliten durch Interferone.

Schlussfolgerung

Die Bedeutung mikroglialer Aktivierung sowie die therapeutische Beeinflussung von Mikroglia mit dem Ziel der Neuroprotektion sind zuletzt immer mehr in den Fokus gerückt und sollen in diesem Übersichtsartikel genauer beleuchtet werden.

Summary

Objective

Microglia are the resident macrophages of the CNS and important for the maintenance of defence mechanisms in the CNS and the phagocytosis of apoptotic cells and cell debris. There is increasing evidence pointing towards a crucial influence of microglia for the pathogenesis of multiple sclerosis (MS).

Materials and Methods

We performed a PubMed data base search to include relevant articles.

Results

MS is characterized by a damage of the myelin sheath with consecutive demyelination and often axonal destruction. This is mediated by inflammatory processes with microglial involvement by release of reactive oxygen and nitrogen species as well as pro-inflammatory cytokines such as IL-1beta and TNF-alpha. Microglia can present different states of activation, such as a state of classical activation, characterized by an inflammatory cytokine pattern (M1) and a state of alternative activation, characterized by a neuroprotective pattern (M2). Therapeutically different mechanisms exist which can be modulated such as the Nrf2 pathway with dimethylfumarate or the decreased microglial release of reactive oxygen species by interferon.

Conclusions

The importance of microglial activation and the therapeutic modulation of MG to a neuroprotective state get further into focus of MStherapy and will be elucidated in this review.

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