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Regulation of survival motor neuron protein by the nuclear factor-kappa B pathway in mouse spinal cord motoneurons

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Issue date
2017-08-14
Author
Arumugam, Saravanan
Tasheva, Stefka Mincheva
Periyakaruppiah, Ambika
Fuente Ruiz, Sandra de la
Soler i Tatché, Rosa Ma.
Garcera, Ana
Suggested citation
Arumugam, Saravanan; Tasheva, Stefka Mincheva; Periyakaruppiah, Ambika; Fuente Ruiz, Sandra de la; Soler i Tatché, Rosa Ma.; Garcera, Ana; . (2017) . Regulation of survival motor neuron protein by the nuclear factor-kappa B pathway in mouse spinal cord motoneurons. Molecular Neurobiology, 2018, vol. 55, núm. 6, p. 5019-5030. https://doi.org/10.1007/s12035-017-0710-4.
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Abstract
Survival motor neuron (SMN) protein deficiency causes the genetic neuromuscular disorder spinal muscular atrophy (SMA), characterized by spinal cord motoneuron degeneration. Since SMN protein level is critical to disease onset and severity, analysis of the mechanisms involved in SMN stability is one of the central goals of SMA research. Here, we describe the role of several members of the NF-κB pathway in regulating SMN in motoneurons. NF-κB is one of the main regulators of motoneuron survival and pharmacological inhibition of NF-κB pathway activity also induces mouse survival motor neuron (Smn) protein decrease. Using a lentiviral-based shRNA approach to reduce the expression of several members of NF-κB pathway, we observed that IKK and RelA knockdown caused Smn reduction in mouse-cultured motoneurons whereas IKK or RelB knockdown did not. Moreover, isolated motoneurons obtained from the severe SMA mouse model showed reduced protein levels of several NF-κB members and RelA phosphorylation. We describe the alteration of NF-κB pathway in SMA cells. In the context of recent studies suggesting regulation of altered intracellular pathways as a future pharmacological treatment of SMA, we propose the NF-κB pathway as a candidate in this new therapeutic approach.
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http://hdl.handle.net/10459.1/63058
DOI
https://doi.org/10.1007/s12035-017-0710-4
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Molecular Neurobiology, 2018, vol. 55, núm. 6, p. 5019-5030
European research projects
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