Caspase inhibition reduces apoptosis and increases survival of nigral transplants

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1999
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Schierle, Gabriele S.
Hansson, Oskar
Widner, Håkan
Brundin, Patrik
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Transplantation of embryonic nigral tissue ameliorates functional deficiencies in Parkinson disease. The main practical constraints of neural grafting are the shortage of human donor tissue and the poor survival of dopaminergic neurons grafted into patients, which is estimated at 5−10% (refs.). The required amount of human tissue could be considerably reduced if the neuronal survival was augmented. Studies in rats indicate that most implanted embryonic neurons die within 1 week of transplantation, and that most of this cell death is apoptotic6. Modified peptides, such as acetyl−tyrosinyl−valyl−alanyl−aspartyl−chloro−
methylketone (Ac−YVAD−cmk), that specifically inhibit proteases of the caspase family effectively block apoptosis in a plethora of experimental paradigms, such as growth factor withdrawal, excitotoxicity, axotomy, cerebral ischemia and brain trauma. Here we examined the effects of caspase inhibition by Ac−YVAD−cmk on cell death immediately after donor tissue preparation and on long−term graft survival. Treatment of the embryonic nigral cell suspension with Ac−YVAD−cmk mitigated DNA fragmentation and reduced apoptosis in transplants. It also increased survival of dopaminergic neurons grafted to hemiparkinsonian rats, and thereby substantially improved functional recovery.

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ISO 690SCHIERLE, Gabriele S., Oskar HANSSON, Marcel LEIST, Pierluigi NICOTERA, Håkan WIDNER, Patrik BRUNDIN, 1999. Caspase inhibition reduces apoptosis and increases survival of nigral transplants. In: Nature Medicine. 1999, 5(1), pp. 97-100. ISSN 1078-8956. Available under: doi: 10.1038/4785
BibTex
@article{Schierle1999-01Caspa-16746,
  year={1999},
  doi={10.1038/4785},
  title={Caspase inhibition reduces apoptosis and increases survival of nigral transplants},
  number={1},
  volume={5},
  issn={1078-8956},
  journal={Nature Medicine},
  pages={97--100},
  author={Schierle, Gabriele S. and Hansson, Oskar and Leist, Marcel and Nicotera, Pierluigi and Widner, Håkan and Brundin, Patrik}
}
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