Caspase inhibition reduces apoptosis and increases survival of nigral transplants
Schierle, Gabriele LU ; Hansson, Oskar LU
; Leist, M
; Nicotera, P
; Widner, Håkan
LU
and Brundin, Patrik
LU
(1999)
In Nature Medicine
5(1).
p.97-100
- Abstract
- 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. 3,4). 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 apoptotic. 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... (More)
- 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. 3,4). 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 apoptotic. 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1114606
- author
- Schierle, Gabriele
LU
; Hansson, Oskar
LU
; Leist, M
; Nicotera, P
; Widner, Håkan
LU
and Brundin, Patrik
LU
- organization
- publishing date
- 1999
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Medicine
- volume
- 5
- issue
- 1
- pages
- 97 - 100
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:9883846
- scopus:0033008216
- ISSN
- 1546-170X
- DOI
- 10.1038/4785
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neurology, Lund (013027000), Psychiatry/Primary Care/Public Health (013240500), Department of Experimental Medical Science (013210000)
- id
- 14fb8e03-a38f-4991-8464-bc5b21b8abc9 (old id 1114606)
- date added to LUP
- 2016-04-01 15:51:18
- date last changed
- 2022-04-30 17:11:12
@article{14fb8e03-a38f-4991-8464-bc5b21b8abc9,
abstract = {{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. 3,4). 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 apoptotic. 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.}},
author = {{Schierle, Gabriele and Hansson, Oskar and Leist, M and Nicotera, P and Widner, Håkan and Brundin, Patrik}},
issn = {{1546-170X}},
language = {{eng}},
number = {{1}},
pages = {{97--100}},
publisher = {{Nature Publishing Group}},
series = {{Nature Medicine}},
title = {{Caspase inhibition reduces apoptosis and increases survival of nigral transplants}},
url = {{http://dx.doi.org/10.1038/4785}},
doi = {{10.1038/4785}},
volume = {{5}},
year = {{1999}},
}