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Dtsch Med Wochenschr 2004; 129(8): 391-395
DOI: 10.1055/s-2004-819899
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Pathophysiologie / Onkologie
© Georg Thieme Verlag Stuttgart · New York

Proteasen in Malignomen

Bedeutung für Pathogenese und mögliche therapeutische KonsequenzenProteases in malignant tumorsTheir significance for the pathogenesis and possible therapeutic applicationsE. Fröhlich1
  • 1Anatomisches Institut, Universität Tübingen
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Publication History

eingereicht: 26.6.2003

akzeptiert: 7.11.2003

Publication Date:
11 February 2004 (online)

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Proteasen sind an einer Fülle von Stoffwechselvorgängen insbesondere bei Gerinnung, Entzündung, Entwicklung und Apoptose beteiligt. Auch bei zahlreichen Erkrankungen spielen sie in der Pathogenese eine entscheidende Rolle. So sind einige erbliche Erkrankungen bekannt, die auf erhöhter Proteaseaktivität beruhen. Am bekanntesten sind das Lungenemphysem (α-1-Antitrypsin-Inhibitor Defekt, 14) und das angioneurotische Ödem (C1-Esterase-Inhibitor Defekt, 4). Allerdings sind diese Erkrankungen eher selten. Wesentlich häufiger sind nicht erblich bedingte Veränderungen der Proteaseaktivität, beispielsweise bei rheumatischen Erkrankungen und bei Malignomen. Im Folgenden soll insbesondere auf die Rolle der Proteasen im Malignomgeschehen eingegangen werden. Die selektive Hemmung bestimmter Proteaseaktivitäten stellt prinzipiell eine Therapiemöglichkeit für Malignome dar. Leider haben derartige Therapieversuche bislang nicht den gewünschten Erfolg gebracht. Im Folgenden soll dargestellt werden, wo die Probleme und Chancen eines Eingriffs in das Proteasesystem bei Tumoren liegen.

Proteasen werden nach verschiedenen Gesichtspunkten eingeteilt: nach

Art der Spaltung im Protein (Abspaltung vom aminoterminalen oder vom carboxyterminalen Ende des Proteins), der topographischen Verteilung des Enzyms in der Zelle (im Zytosol, membranassoziiert oder in Lysosomen enthalten), dem aktiven Zentrum.

Letztere Einteilung ist im Hinblick auf Funktion und Inhibition der Proteasen besonders zweckmäßig und wird daher bevorzugt verwendet.

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Priv.-Doz. Dr. med. Eleonore Fröhlich

Anatomisches Institut, Eberhard-Karls-Universität Tübingen

Österbergstraße 3

72074 Tübingen