Mutant huntingtin can paradoxically protect neurons from death
(2008) In Cell Death and Differentiation 15(3). p.435-442- Abstract
- Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a mutation in the gene huntingtin and characterized by motor, cognitive and psychiatric symptoms. Huntingtin contains a CAG repeat in exon 1. An expansion of this CAG repeat above 35 results in misfolding of Huntingtin, giving rise to protein aggregates and neuronal cell death. There are several transgenic HD mouse models that reproduce most of the features of the human disorder, for example protein inclusions, some neurodegeneration as well as motor and cognitive symptoms. At the same time, a subgroup of the HD transgenic mouse models exhibit dramatically reduced susceptibility to excitotoxicity. The mechanism behind this is unknown. Here, we review the... (More)
- Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a mutation in the gene huntingtin and characterized by motor, cognitive and psychiatric symptoms. Huntingtin contains a CAG repeat in exon 1. An expansion of this CAG repeat above 35 results in misfolding of Huntingtin, giving rise to protein aggregates and neuronal cell death. There are several transgenic HD mouse models that reproduce most of the features of the human disorder, for example protein inclusions, some neurodegeneration as well as motor and cognitive symptoms. At the same time, a subgroup of the HD transgenic mouse models exhibit dramatically reduced susceptibility to excitotoxicity. The mechanism behind this is unknown. Here, we review the literature regarding this phenomenon, attempt to explain what protein domains are crucial for this phenomenon and point toward a putative mechanism. We suggest, that the C-terminal domain of exon 1 Huntingtin, namely the proline rich domain, is responsible for mediating a neuroprotective effect against excitotoxicity. Furthermore, we point out the possible importance of this mechanism for future therapies in neurological disorders that have been suggested to be associated with excitotoxicity, for example Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1196951
- author
- Zuchner, T and Brundin, Patrik LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- domain, neuroprotection, proline rich, NMDA, excitotoxicity, Huntington's disease, Huntingtin
- in
- Cell Death and Differentiation
- volume
- 15
- issue
- 3
- pages
- 435 - 442
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000253239900002
- scopus:39449105711
- ISSN
- 1350-9047
- DOI
- 10.1038/sj.cdd.4402261
- 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: Neuronal Survival (013212041)
- id
- f836bba5-9e9d-467b-99c4-8280bce33bdd (old id 1196951)
- date added to LUP
- 2016-04-01 11:39:14
- date last changed
- 2022-01-26 08:11:17
@article{f836bba5-9e9d-467b-99c4-8280bce33bdd,
abstract = {{Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a mutation in the gene huntingtin and characterized by motor, cognitive and psychiatric symptoms. Huntingtin contains a CAG repeat in exon 1. An expansion of this CAG repeat above 35 results in misfolding of Huntingtin, giving rise to protein aggregates and neuronal cell death. There are several transgenic HD mouse models that reproduce most of the features of the human disorder, for example protein inclusions, some neurodegeneration as well as motor and cognitive symptoms. At the same time, a subgroup of the HD transgenic mouse models exhibit dramatically reduced susceptibility to excitotoxicity. The mechanism behind this is unknown. Here, we review the literature regarding this phenomenon, attempt to explain what protein domains are crucial for this phenomenon and point toward a putative mechanism. We suggest, that the C-terminal domain of exon 1 Huntingtin, namely the proline rich domain, is responsible for mediating a neuroprotective effect against excitotoxicity. Furthermore, we point out the possible importance of this mechanism for future therapies in neurological disorders that have been suggested to be associated with excitotoxicity, for example Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.}},
author = {{Zuchner, T and Brundin, Patrik}},
issn = {{1350-9047}},
keywords = {{domain; neuroprotection; proline rich; NMDA; excitotoxicity; Huntington's disease; Huntingtin}},
language = {{eng}},
number = {{3}},
pages = {{435--442}},
publisher = {{Nature Publishing Group}},
series = {{Cell Death and Differentiation}},
title = {{Mutant huntingtin can paradoxically protect neurons from death}},
url = {{http://dx.doi.org/10.1038/sj.cdd.4402261}},
doi = {{10.1038/sj.cdd.4402261}},
volume = {{15}},
year = {{2008}},
}