Regulation of survival motor neuron protein by the nuclear factor-kappa B pathway in mouse spinal cord motoneurons
Tasheva, Stefka Mincheva
MetadataShow full item record
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.
Is part ofMolecular Neurobiology, 2018, vol. 55, núm. 6, p. 5019-5030
Showing items related by title, author, creator and subject.
Periyakaruppiah, Ambika; Fuente Ruiz, Sandra de la; Arumugam, Saravanan; Bahi i Pla, Núria; Garcera, Ana; Soler i Tatché, Rosa Ma. (Elsevier, 2016)SpinalMuscular Atrophy (SMA), a neurodegenerative disorder primarily affecting motoneurons (MNs), is caused by the loss of the Survival Motor Neuron 1 (SMN1) gene and reduced levels of full-length survival motor neuron (SMN) ...
Calpain Inhibition Increases SMN Protein in Spinal Cord Motoneurons and Ameliorates the Spinal Muscular Atrophy Phenotype in Mice Fuente Ruiz, Sandra de la; Sansa Zaragoza, Alba; Periyakaruppiah, Ambika; Garcera, Ana; Soler i Tatché, Rosa Ma. (Springer Verlag, 2018)Spinal muscular atrophy (SMA), a leading genetic cause of infant death, is caused by the loss of survival motor neuron 1 (SMN1) gene. SMA is characterized by the degeneration and loss of spinal cord motoneurons (MNs), ...
Garcera, Ana; Bahi i Pla, Núria; Periyakaruppiah, Ambika; Arumugam, Saravanan; Soler i Tatché, Rosa Ma. (Macmillan Publishers Limited, 2013)Spinal muscular atrophy (SMA) is a genetic disorder characterized by degeneration of spinal cord motoneurons (MNs), resulting in muscular atrophy and weakness. SMA is caused by mutations in the Survival Motor Neuron 1 ...