Caspase inhibition reduces apoptosis and increases survival of nigral transplants


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SCHIERLE, 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. 5(1), pp. 97-100. ISSN 1078-8956. Available under: doi: 10.1038/4785

@article{Schierle1999-01Caspa-16746, title={Caspase inhibition reduces apoptosis and increases survival of nigral transplants}, year={1999}, doi={10.1038/4785}, 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} }

Brundin, Patrik eng Schierle, Gabriele S. Widner, Håkan Leist, Marcel Nicotera, Pierluigi Brundin, Patrik Hansson, Oskar 2011-11-16T08:12:23Z Schierle, Gabriele S. 1999-01 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−<br />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. Hansson, Oskar Nicotera, Pierluigi Leist, Marcel Publ. in: Nature Medicine ; 5 (1999), 1. - pp. 97-100 terms-of-use Widner, Håkan Caspase inhibition reduces apoptosis and increases survival of nigral transplants 2011-11-16T08:12:23Z

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