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Journal of Neuroinflammation

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Open Access 01-12-2015 | Research

Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease

Authors: Elvira Valera, Michael Mante, Scott Anderson, Edward Rockenstein, Eliezer Masliah

Published in: Journal of Neuroinflammation | Issue 1/2015

Abstract

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.

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Title: Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease
Authors: Elvira Valera
Michael Mante
Scott Anderson
Edward Rockenstein
Eliezer Masliah
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2015
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-015-0320-x

At a glance: The STEP trials

Springer Medicine

Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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