scholarly journals Survival of motor neuron 2 centromeric (SMN2; SMNC)

2011 ◽  
Vol 4 (12) ◽  
pp. 342-342
Keyword(s):  
Motor Neuron ◽  
Survival Of Motor Neuron

Description and physical localization of the bovine survival of motor neuron gene (SMN)

1998 ◽  
Vol 83 (1-2) ◽  
pp. 39-42 ◽  
Author(s):  
D. Pietrowski ◽  
T. Goldammer ◽  
S. Meinert ◽  
M. Schwerin ◽  
M. Förster
Keyword(s):  
Motor Neuron ◽  
Survival Of Motor Neuron

scholarly journals Interaction between the small‐nuclear‐RNA cap hypermethylase and the spinal muscular atrophy protein, survival of motor neuron

EMBO Reports ◽  
2003 ◽  
Vol 4 (6) ◽  
pp. 616-622 ◽  
Author(s):  
John Mouaikel ◽  
Usha Narayanan ◽  
Céline Verheggen ◽  
A Gregory Matera ◽  
Edouard Bertrand ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Small Nuclear Rna ◽  
Nuclear Rna ◽  
Survival Of Motor Neuron

scholarly journals Gemin2 Plays an Important Role in Stabilizing the Survival of Motor Neuron Complex

2007 ◽  
Vol 282 (15) ◽  
pp. 11122-11134 ◽  
Author(s):  
Chihiro Ogawa ◽  
Kengo Usui ◽  
Makoto Aoki ◽  
Fuyu Ito ◽  
Masayoshi Itoh ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Survival Of Motor Neuron

scholarly journals Identification of Novel Compounds That Increase SMN Protein Levels Using an Improved SMN2 Reporter Cell Assay

2012 ◽  
Vol 17 (4) ◽  
pp. 481-495 ◽  
Author(s):  
Jonathan J. Cherry ◽  
Matthew C. Evans ◽  
Jake Ni ◽  
Gregory D. Cuny ◽  
Marcie A. Glicksman ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Neurodegenerative Disorder ◽  
Muscular Atrophy ◽  
Full Length ◽  
Reporter Cell ◽  
Protein Levels ◽  
Smn2 Gene ◽  
Smn Protein ◽  
Neuron Function ◽  
Survival Of Motor Neuron

Spinal muscular atrophy (SMA) is a neurodegenerative disorder that is characterized by progressive loss of motor neuron function. It is caused by the homozygous loss of the SMN1 ( survival of motor neuron 1) gene and a decrease in full-length SMN protein. SMN2 is a nearly identical homolog of SMN1 that, due to alternative splicing, expresses predominantly truncated SMN protein. SMN2 represents an enticing therapeutic target. Increasing expression of full-length SMN from the SMN2 gene might represent a treatment for SMA. We describe a newly designed cell-based reporter assay that faithfully and reproducibly measures full-length SMN expression from the SMN2 gene. This reporter can detect increases of SMN protein by an array of compounds previously shown to regulate SMN2 expression and by the overexpression of proteins that modulate SMN2 splicing. It also can be used to evaluate changes at both the transcriptional and splicing level. This assay can be a valuable tool for the identification of novel compounds that increase SMN2 protein levels and the optimization of compounds already known to modulate SMN2 expression. We present here preliminary data from a high-throughput screen using this assay to identify novel compounds that increase expression of SMN2.

scholarly journals A screen for regulators of survival of motor neuron protein levels

2011 ◽  
Vol 7 (8) ◽  
pp. 544-552 ◽  
Author(s):  
Nina R Makhortova ◽  
Monica Hayhurst ◽  
Antonio Cerqueira ◽  
Amy D Sinor-Anderson ◽  
Wen-Ning Zhao ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Protein Levels ◽  
Motor Neuron Protein ◽  
Survival Of Motor Neuron

scholarly journals Newborn Screening for Spinal Muscular Atrophy by Calibrated Short-Amplicon Melt Profiling

2012 ◽  
Vol 58 (6) ◽  
pp. 1033-1039 ◽  
Author(s):  
Steven F Dobrowolski ◽  
Ha T Pham ◽  
Frances Pouch Downes ◽  
Thomas W Prior ◽  
Edwin W Naylor ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Newborn Screening ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Dried Blood Spots ◽  
Continuous Treatment ◽  
Management Options ◽  
Blood Spots ◽  
Survival Of Motor Neuron ◽  
Homozygous Deletions

Abstract BACKGROUND The management options for the autosomal recessive neurodegenerative disorder spinal muscular atrophy (SMA) are evolving; however, their efficacy may require presymptom diagnosis and continuous treatment. To identify presymptomatic SMA patients, we created a DNA-based newborn screening assay to identify the homozygous deletions of the SMN1 (survival of motor neuron 1, telomeric) gene observed in 95%–98% of affected patients. METHODS We developed primers that amplify a 52-bp PCR product from homologous regions in the SMN1 and SMN2 (survival of motor neuron 2, centromeric) genes that flank a divergent site at site c.840. Post-PCR high-resolution melt profiling assessed the amplification product, and we used a unique means of melt calibration to normalize profiles. Samples that we had previously characterized for the numbers of SMN1 and SMN2 copies established genotypes associated with particular profiles. The system was evaluated with approximately 1000 purified DNA samples, 100 self-created dried blood spots, and >1200 dried blood spots from newborn screening tests. RESULTS Homozygous deletion of SMN1 exon 7 produced a distinctive melt profile that identified SMA patients. Samples with different numbers of SMN1 and SMN2 copies were resolved by their profiles. All samples with homozygous deletions were unambiguously recognized, and no normal sample was misidentified as a positive. CONCLUSIONS This assay has characteristics suitable for population-based screening. A reliable screening test will facilitate the identification of an SMA-affected cohort to receive early intervention to maximize the benefit from treatment. A prospective screening trial will allow the efficacy of treatment options to be assessed, which may justify the inclusion of SMA as a target for population screening.

scholarly journals The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein

2013 ◽  
Vol 24 (12) ◽  
pp. 1863-1871 ◽  
Author(s):  
Deborah Y. Kwon ◽  
Maria Dimitriadi ◽  
Barbara Terzic ◽  
Casey Cable ◽  
Anne C. Hart ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Ubiquitin Ligase ◽  
Cultured Cells ◽  
Muscular Atrophy ◽  
E3 Ubiquitin Ligase ◽  
Proteasome Inhibition ◽  
Protein Levels ◽  
Smn Protein ◽  
Survival Of Motor Neuron

Spinal muscular atrophy is an inherited motor neuron disease that results from a deficiency of the survival of motor neuron (SMN) protein. SMN is ubiquitinated and degraded through the ubiquitin proteasome system (UPS). We have previously shown that proteasome inhibition increases SMN protein levels, improves motor function, and reduces spinal cord, muscle, and neuromuscular junction pathology of spinal muscular atrophy (SMA) mice. Specific targets in the UPS may be more efficacious and less toxic. In this study, we show that the E3 ubiquitin ligase, mind bomb 1 (Mib1), interacts with and ubiquitinates SMN and facilitates its degradation. Knocking down Mib1 levels increases SMN protein levels in cultured cells. Also, knocking down the Mib1 orthologue improves neuromuscular function in Caenorhabditis elegans deficient in SMN. These findings demonstrate that Mib1 ubiquitinates and catalyzes the degradation of SMN, and thus represents a novel therapeutic target for SMA.

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