Therapeutic approaches to spinal and bulbar muscular atrophy.
(2010) In Trends in Pharmacological Sciences Okt. p.523-527- Abstract
- Spinal and bulbar muscular atrophy is a hereditary motor neuron disease caused by trinucleotide repeat expansion in the androgen receptor gene. The disease mechanism probably involves a toxic gain of function in the mutant protein, because other mutations that cause a loss of androgen receptor function result in a different phenotype and the mutant protein is toxic in mouse models. In these models, the toxicity is ligand-dependent and is associated with protein aggregation, as well as altered transcriptional regulation, axonal transport and mitochondrial function. Various therapeutic approaches have shown efficacy in mouse models, including androgen reduction, heat shock protein 90 (HSP90) inhibition and insulin-like growth factor (IGF)-1... (More)
- Spinal and bulbar muscular atrophy is a hereditary motor neuron disease caused by trinucleotide repeat expansion in the androgen receptor gene. The disease mechanism probably involves a toxic gain of function in the mutant protein, because other mutations that cause a loss of androgen receptor function result in a different phenotype and the mutant protein is toxic in mouse models. In these models, the toxicity is ligand-dependent and is associated with protein aggregation, as well as altered transcriptional regulation, axonal transport and mitochondrial function. Various therapeutic approaches have shown efficacy in mouse models, including androgen reduction, heat shock protein 90 (HSP90) inhibition and insulin-like growth factor (IGF)-1 overexpression. Clinical trials of androgen-reducing agents have had mixed results, with indications of efficacy but no proof of clinically meaningful benefit to date. These clinical studies have established outcome measures for future trials of other agents that have been beneficial in animal studies. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1687940
- author
- Ranganathan, Srikanth LU and Fischbeck, Kenneth H
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Trends in Pharmacological Sciences
- volume
- Okt
- pages
- 523 - 527
- publisher
- Elsevier
- external identifiers
-
- wos:000284499900004
- pmid:20863580
- scopus:77958150581
- pmid:20863580
- ISSN
- 0165-6147
- DOI
- 10.1016/j.tips.2010.08.005
- 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
- 4c30a809-05ea-424f-aa4d-b9d29fbe2f2c (old id 1687940)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/20863580?dopt=Abstract
- date added to LUP
- 2016-04-04 09:42:40
- date last changed
- 2022-01-29 19:10:26
@article{4c30a809-05ea-424f-aa4d-b9d29fbe2f2c,
abstract = {{Spinal and bulbar muscular atrophy is a hereditary motor neuron disease caused by trinucleotide repeat expansion in the androgen receptor gene. The disease mechanism probably involves a toxic gain of function in the mutant protein, because other mutations that cause a loss of androgen receptor function result in a different phenotype and the mutant protein is toxic in mouse models. In these models, the toxicity is ligand-dependent and is associated with protein aggregation, as well as altered transcriptional regulation, axonal transport and mitochondrial function. Various therapeutic approaches have shown efficacy in mouse models, including androgen reduction, heat shock protein 90 (HSP90) inhibition and insulin-like growth factor (IGF)-1 overexpression. Clinical trials of androgen-reducing agents have had mixed results, with indications of efficacy but no proof of clinically meaningful benefit to date. These clinical studies have established outcome measures for future trials of other agents that have been beneficial in animal studies.}},
author = {{Ranganathan, Srikanth and Fischbeck, Kenneth H}},
issn = {{0165-6147}},
language = {{eng}},
pages = {{523--527}},
publisher = {{Elsevier}},
series = {{Trends in Pharmacological Sciences}},
title = {{Therapeutic approaches to spinal and bulbar muscular atrophy.}},
url = {{http://dx.doi.org/10.1016/j.tips.2010.08.005}},
doi = {{10.1016/j.tips.2010.08.005}},
volume = {{Okt}},
year = {{2010}},
}