Regulation of Survival Motor Neuron Protein by the Nuclear Factor-Kappa B Pathway in Mouse Spinal Cord Motoneurons

Saravanan Arumugam, Stefka Tasheva, Ambika Periyakaruppiah, Sandra de la Fuente, Rosa M. Soler, Ana Garcera

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5019-5030
Number of pages12
JournalMolecular Neurobiology
Volume55
Issue number6
DOIs
Publication statusPublished or Issued - 1 Jun 2018
Externally publishedYes

Keywords

  • Motoneurons
  • NF-kappaB
  • RelA
  • SMN
  • Spinal muscular atrophy

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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