A SMNΔ7 read-through product confers functionality to the SMNΔ7 protein
Section snippets
Acknowledgements
V.B.M. is supported by the Clinical BioDectives Program (NIH T90 DK070105). This work was funded by grants from Phi Zeta-Pi Chapter Research Grant (V.B.M.), FightSMA (C.L.L.), the Muscular Dystrophy Association (C.L.L.) and the National Institutes of Health (C.L.L, R01 NS41584; R01 HD054413).
References (23)
- et al.
Restoration of SMN function: delivery of a trans-splicing RNA re-directs SMN2 pre-mRNA splicing
Mol. Ther.
(2007) - et al.
The neurobiology of childhood spinal muscular atrophy
Neurobiol. Dis.
(1996) - et al.
The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis
Cell
(1997) - et al.
Identification and characterization of a spinal muscular atrophy-determining gene
Cell
(1995) - et al.
Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism
Chem. Biol.
(2004) - et al.
The SMN complex, an assemblyosome of ribonucleoproteins
Curr. Opin. Cell Biol.
(2002) Therapeutics development for spinal muscular atrophy
NeuroRx
(2006)- et al.
Smn depletion alters profilin II expression and leads to upregulation of the RhoA/ROCK pathway and defects in neuronal integrity
J. Mol. Neurosci.
(2007) - et al.
Survival motor neuron function in motor axons is independent of functions required for small nuclear ribonucleoprotein biogenesis
J. Neurosci.
(2006) - et al.
Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1
Nat. Genet.
(2002)
The survival motor neuron protein in spinal muscular atrophy
Hum. Mol. Genet.
Cited by (33)
Spinal muscular atrophy
2018, Handbook of Clinical NeurologyCitation Excerpt :Given the challenges of blood–brain barrier penetrability facing other current strategies, this series of orally bioavailable compounds presents a promising potential therapy for SMA patients. Another approach to increasing SMN2 expression is through the use of aminoglycosides to force “read through” past the stop codon of the SMNΔ7 transcript, producing an artificially elongated protein product that is comparatively more stable and functional than the SMNΔ7 protein (Mattis et al., 2008). Treatment of cells (Mattis et al., 2006) and mice (Mattis et al., 2009, 2012) with these compounds showed increased SMN protein and improved neuromuscular phenotype.
Small Molecule Approaches to Upregulate SMN Expression From the SMN2 Locus
2017, Spinal Muscular Atrophy: Disease Mechanisms and TherapyMammalian Models of Spinal Muscular Atrophy
2017, Spinal Muscular Atrophy: Disease Mechanisms and TherapySpinal muscular atrophy: An update on therapeutic progress
2013, Biochimica et Biophysica Acta - Molecular Basis of DiseaseGene therapy for amyotrophic lateral sclerosis
2012, Neurobiology of DiseaseAnalysis of a read-through promoting compound in a severe mouse model of spinal muscular atrophy
2012, Neuroscience LettersCitation Excerpt :This could be due to the small increase in gross motor function, seen by the TTR testing, denoting the ability of these severe mice to feed better. It has been shown that SMNΔ7 protein has severely reduced functionality when compared to full-length SMN [1,15], assumedly due mostly to its instability [2] and inability to interact with members of the Gemin complex [2], known to be crucial in SMN's most well-studied role in UsnRNP biogenesis. Therefore, it is completely logical that if SMNΔ7 could regain its stability to self-associate and associate with its complex, it would regain its functionality.