Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy

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Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy.

The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by mutation of the telomeric survival motor neuron 1 (SMN1) gene with retention of the centromeric SMN2 gene. We sought to establish whether the potent and specific hydroxamic acid class of histone deacetylase (HDAC) inhibitors activates SMN2 gene expression in vivo and modulates the SMA disease phenotype when delivered ...

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Human Growth Hormone Increases SMN Expression and Survival in Severe Spinal Muscular Atrophy Mouse Model.

BACKGROUND Autosomal recessive spinal muscle atrophy (SMA) is characterized by the loss of α motor neurons resulting in progressive muscle loss and respiratory failure. SMA is one of the most common inherited causes of infant death with a carrier frequency of 1 in 50 and a calculated prevalence of about 1 in 11,000 live births in the US. The low amount of functional survival motor neuron (SMN) ...

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Prolactin increases SMN expression and survival in a mouse model of severe spinal muscular atrophy via the STAT5 pathway.

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that is characterized by the loss of motor neurons, resulting in progressive muscle atrophy. It is caused by the loss of functional survival motor neuron (SMN) protein due to mutations or deletion in the SMN1 gene. A potential treatment strategy for SMA is to upregulate levels of SMN protein. Several agents that a...

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Celecoxib increases SMN and survival in a severe spinal muscular atrophy mouse model via p38 pathway activation.

The loss of functional Survival Motor Neuron (SMN) protein due to mutations or deletion in the SMN1 gene causes autosomal recessive neurodegenerative spinal muscle atrophy (SMA). A potential treatment strategy for SMA is to upregulate the amount of SMN protein originating from the highly homologous SMN2 gene, compensating in part for the absence of the functional SMN1 gene. We have previously s...

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The Smn-Independent Beneficial Effects of Trichostatin A on an Intermediate Mouse Model of Spinal Muscular Atrophy

Spinal muscular atrophy is an autosomal recessive neuromuscular disease characterized by the progressive loss of alpha motor neurons in the spinal cord. Trichostatin A (TSA) is a histone deacetylase inhibitor with beneficial effects in spinal muscular atrophy mouse models that carry the human SMN2 transgene. It is currently unclear whether TSA specifically targets the SMN2 gene or whether other...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2007

ISSN: 0021-9738

DOI: 10.1172/jci29562