|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
SMN protein is expressed from two genes, SMN1 and SMN2, but the SMN1 gene is homozygously disrupted in people with spinal muscular atrophy; as a consequence, all of the SMN that is expressed in people with this disease is from the SMN2 gene.
|
28728573 |
2017 |
|
Spinal Muscular Atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Mutations in SMN could affect several molecular processes, among which aberrant pre-mRNA splicing caused by defective snRNP biogenesis is hypothesized as a major cause of SMA.
|
25483032 |
2014 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
SMN2, however, can also produce some functional SMN to partially compensate for loss of SMN1 in SMA suggesting increasing transcription of SMN2 as a potential therapy to treat patients with SMA.
|
25514431 |
2014 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Here, we discuss recent advances in basic and clinical studies toward finding safe and effective treatments of spinal muscular atrophy using gene therapy, antisense oligonucleotides, and other small molecule modulators of SMN expression.
|
26173388 |
2016 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Spinal muscular atrophy is caused by reduced levels of the survival of motor neurons (SMN) protein.
|
17640370 |
2007 |
|
Spinal Muscular Atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Spinal muscular atrophy (SMA) is caused by homozygous survival of motor neurons 1 (SMN1) gene deletions, leaving a duplicate gene, SMN2, as the sole source of SMN protein.
|
20194437 |
2010 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival motor neuron (SMN) protein.
|
17895963 |
2007 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
These results clearly suggested that cellular SMN proteins regulated miR-9 expression and that miR-9 expression was related to SMA severity.
|
24751385 |
2014 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein leading to muscle paralysis and respiratory failure.
|
20085811 |
2010 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Reduced SMN protein levels in SMA patients lead to progressive degeneration of spinal motor neurons (MNs).
|
30667343 |
2019 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Low levels of full-length survival motor neuron (SMN) protein cause the motor neuron disease, spinal muscular atrophy (SMA).
|
21840928 |
2011 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
In SMA patients, the loss of SMN1 but the presence of SMN2 results in low levels of full-length SMN transcript and therefore low SMN protein levels which causes SMA.
|
10369862 |
1999 |
|
Spinal Muscular Atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The survival of motor neurons (SMN) gene, the SMA disease gene, is homozygously deleted or mutated in more than 98% of SMA patients.
|
10500148 |
1999 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The SMN protein is highly expressed within brain, spinal cord and muscle, and is decreased in SMA patients.
|
12847076 |
2003 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
One prominent example is spinal muscular atrophy (SMA), a monogenic, neuromuscular disorder caused by reduced levels of functional survival motor neuron (SMN) protein.
|
19286363 |
2009 |
|
Spinal Muscular Atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Linkage studies, as well as the analysis of the SMN gene, recognised that SMA variants (with severe arthogryposis or cerebellar or diaphragmatic involvement) are not linked to chromosome 5q markers.
|
9185186 |
1997 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Western blot analysis of fibroblasts from SMA patients with various clinical severities of SMA showed a moderate reduction in the amount of SMN protein, particularly in type I (most severe) patients.
|
9259265 |
1997 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Given that SMN2 is regarded as a target for potential pharmacological therapies in SMA, the identification of genetic factors other than the SMN genes is necessary to better understand the pathogenesis of the disease in order to implement additional therapeutic approaches.
|
15981080 |
2006 |
|
Spinal Muscular Atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In contrast, most chronic SMA patients have at least one SMA allele with either an intragenic SMN(T) deletion or a SMN(C):SMN(T) chimeric gene which replaces the normal SMN(T) gene.
|
9295075 |
1997 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
However, the molecular pathway linking marked deficiency of SMN to SMA phenotype remains unclear.
|
16118268 |
2006 |
|
Spinal Muscular Atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Two almost identical SMN genes are present on 5q13: the SMN1 gene, which is the spinal muscular atrophy-determining gene, and the SMN2 gene.
|
21673580 |
2011 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Such observations provide motivation to investigate possible transport defects or inefficiency of SMN associated RNPs in motor neuron axons in SMA.
|
12878704 |
2003 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Spinal muscular atrophy (SMA) is a lethal human disease characterized by motor neuron dysfunction and muscle deterioration due to depletion of the ubiquitous survival motor neuron (SMN) protein.
|
23063130 |
2012 |
|
Spinal Muscular Atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Here, we characterize two novel compounds that increased SMN protein levels in both reporter cells and SMA fibroblasts and show that one increases lifespan, motor function, and SMN protein levels in a severe mouse model of SMA.
|
23740718 |
2013 |
|
Spinal Muscular Atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Splicing changes in SMA mouse motoneurons and SMN-depleted neuroblastoma cells: evidence for involvement of splicing regulatory proteins.
|
25692239 |
2014 |