Apoptosis in Caspase-inhibited Neurons

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2001
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Volbracht, Christiane
Kolb, Stefan A.
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Molecular Medicine. 2001, 7(1), pp. 36-48
Zusammenfassung

Background: There is growing evidence of apoptosis in neurodegenerative disease. However, it is still unclear whether the pathological manifestations observed in slow neurodegenerative diseases are due to neuronal loss or whether they are related to independent degenerative events in the axodendritic network. It also remains elusive whether a single, caspase-based executing system involving caspases is responsible for neuronal loss by apoptosis. Materials and Methods: Long-term exposure to the microtubule-disassembling agent, colchicine, was used to disrupt the axodendritic network and eventually trigger caspase-3-mediated apoptosis in cultures of cerebellar granule cells. For this model, we investigated the role of Bcl-2 and caspases in neurite degeneration and death of neuronal somata. Results: Early degeneration of the axodendritic network occurred by a Bcl-2 and caspase-independent mechanism. Conversely, apoptosis of the cell body was delayed by Bcl-2 and initially blocked by caspase inhibition. However, when caspase activity was entirely blocked by zVAD-fmk, colchicine-exposed neurons still underwent delayed cell death characterized by cytochrome c release, chromatin condensation to irregularly shaped clumps, DNA-fragmentation, and exposure of phosphatidylserine. Inhibitors of the proteasome reduced these caspase-independent apoptotic-like features of the neuronal soma. Conclusion: Our data suggest that Bcl-2 dependent and caspase-mediated death programs account only partially for neurodegenerative changes in injured neurons. Blockage of the caspase execution machinery may only temporarily rescue damaged neurons and classical apoptotic features can still appear in caspase-inhibited neurons.

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570 Biowissenschaften, Biologie
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ISO 690VOLBRACHT, Christiane, Marcel LEIST, Stefan A. KOLB, Pierluigi NICOTERA, 2001. Apoptosis in Caspase-inhibited Neurons. In: Molecular Medicine. 2001, 7(1), pp. 36-48
BibTex
@article{Volbracht2001Apopt-6901,
  year={2001},
  title={Apoptosis in Caspase-inhibited Neurons},
  number={1},
  volume={7},
  journal={Molecular Medicine},
  pages={36--48},
  author={Volbracht, Christiane and Leist, Marcel and Kolb, Stefan A. and Nicotera, Pierluigi}
}
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