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Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease
BACKGROUND: Parkinson’s disease (PD) is one of the most common causes of dementia and motor deficits in the elderly. PD is characterized by the abnormal accumulation of the synaptic protein alpha-synuclein (α-syn) and degeneration of dopaminergic neurons in substantia nigra, which leads to neurodege...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432827/ https://www.ncbi.nlm.nih.gov/pubmed/25966683 http://dx.doi.org/10.1186/s12974-015-0320-x |
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author | Valera, Elvira Mante, Michael Anderson, Scott Rockenstein, Edward Masliah, Eliezer |
author_facet | Valera, Elvira Mante, Michael Anderson, Scott Rockenstein, Edward Masliah, Eliezer |
author_sort | Valera, Elvira |
collection | PubMed |
description | BACKGROUND: Parkinson’s disease (PD) is one of the most common causes of dementia and motor deficits in the elderly. PD is characterized by the abnormal accumulation of the synaptic protein alpha-synuclein (α-syn) and degeneration of dopaminergic neurons in substantia nigra, which leads to neurodegeneration and neuroinflammation. Currently, there are no disease modifying alternatives for PD; however, targeting neuroinflammation might be a viable option for reducing motor deficits and neurodegeneration. Lenalidomide is a thalidomide derivative designed for reduced toxicity and increased immunomodulatory properties. Lenalidomide has shown protective effects in an animal model of amyotrophic lateral sclerosis, and its mechanism of action involves modulation of cytokine production and inhibition of NF-κB signaling. METHODS: In order to assess the effect of lenalidomide in an animal model of PD, mThy1-α-syn transgenic mice were treated with lenalidomide or the parent molecule thalidomide at 100 mg/kg for 4 weeks. RESULTS: Lenalidomide reduced motor behavioral deficits and ameliorated dopaminergic fiber loss in the striatum. This protective action was accompanied by a reduction in microgliosis both in striatum and hippocampus. Central expression of pro-inflammatory cytokines was diminished in lenalidomide-treated transgenic animals, together with reduction in NF-κB activation. CONCLUSION: These results support the therapeutic potential of lenalidomide for reducing maladaptive neuroinflammation in PD and related neuropathologies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0320-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4432827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44328272015-05-16 Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease Valera, Elvira Mante, Michael Anderson, Scott Rockenstein, Edward Masliah, Eliezer J Neuroinflammation Research BACKGROUND: Parkinson’s disease (PD) is one of the most common causes of dementia and motor deficits in the elderly. PD is characterized by the abnormal accumulation of the synaptic protein alpha-synuclein (α-syn) and degeneration of dopaminergic neurons in substantia nigra, which leads to neurodegeneration and neuroinflammation. Currently, there are no disease modifying alternatives for PD; however, targeting neuroinflammation might be a viable option for reducing motor deficits and neurodegeneration. Lenalidomide is a thalidomide derivative designed for reduced toxicity and increased immunomodulatory properties. Lenalidomide has shown protective effects in an animal model of amyotrophic lateral sclerosis, and its mechanism of action involves modulation of cytokine production and inhibition of NF-κB signaling. METHODS: In order to assess the effect of lenalidomide in an animal model of PD, mThy1-α-syn transgenic mice were treated with lenalidomide or the parent molecule thalidomide at 100 mg/kg for 4 weeks. RESULTS: Lenalidomide reduced motor behavioral deficits and ameliorated dopaminergic fiber loss in the striatum. This protective action was accompanied by a reduction in microgliosis both in striatum and hippocampus. Central expression of pro-inflammatory cytokines was diminished in lenalidomide-treated transgenic animals, together with reduction in NF-κB activation. CONCLUSION: These results support the therapeutic potential of lenalidomide for reducing maladaptive neuroinflammation in PD and related neuropathologies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0320-x) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-14 /pmc/articles/PMC4432827/ /pubmed/25966683 http://dx.doi.org/10.1186/s12974-015-0320-x Text en © Valera et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Valera, Elvira Mante, Michael Anderson, Scott Rockenstein, Edward Masliah, Eliezer Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease |
title | Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease |
title_full | Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease |
title_fullStr | Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease |
title_full_unstemmed | Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease |
title_short | Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease |
title_sort | lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of parkinson’s disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432827/ https://www.ncbi.nlm.nih.gov/pubmed/25966683 http://dx.doi.org/10.1186/s12974-015-0320-x |
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