Zusammenfassung
Die Apoptose stellt einen regulierten Zelltod dar, der zur Aufrechterhaltung der Homeostase in multizellulären Organismen von großer Bedeutung ist. Zahlreiche Signalwege modellieren diese Form des Zelltods. Die Apoptose kann über einen extrinsischen Weg initiiert werden, der – durch Todesrezeptoren vermittelt – eine Kaskade verschiedener Caspasen in der Zelle im Gang setzt und zum Zelltod führt. Intrazelluläre Schädigungen können sich auch über einen intrinsischen Apoptoseweg weiter verselbständigen, der auf dem Boden amplifizierter Proteine insbesondere Cytochrom C aus Mitochondrien freisetzt und so Caspasen aktiviert. Schädigen genetische Veränderungen während eines Transformationsprozesses wiederkehrend physiologische „Checkpoints“, die im physiologischen Zustand eine Apoptose in einer Zelle auslösen, so ist es denkbar, dass Tumorzellen von den Defekten in ihren apoptotischen Signalwegen direkt abhängen, um zu überleben. In diesem Zusammenhang stellen apoptotische Signalwege hervorragende molekulare Ziele für eine rationale Entwicklung neuer therapeutischer Substanzen dar, um eine Apoptose in Tumorzellen spezifisch zu fördern.
Abstract
Apoptosis is a highly regulated pathway that is critical for maintaining homeostasis in multicellular organisms. Numerous signals are capable of modulating cell death. Apoptosis can be initiated through an extrinsic pathway engaging death receptors, which often trigger a caspase cascade that is capable of killing the cell. Intracellular damage proceeds through an intrinsic pathway of apoptosis that relies on amplification loops, especially the release of cytochrome C from the mitochondrion to further activate caspases. If genetic events inherent to the transformation process always violate physiologic checkpoints that would trigger apoptosis, it is conceivable that cancer cells will prove to be addicted to their apoptotic defects for their own maintenance. In this context, apoptotic pathways provide exciting molecular targets for the rational design of new therapeutic agents to specifically promote apoptosis of cancer cells.
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Waaga-Gasser, A. Apoptoseinduktion als Wirkprinzip. Onkologe 13, 250–255 (2007). https://doi.org/10.1007/s00761-006-1171-y
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DOI: https://doi.org/10.1007/s00761-006-1171-y