• Corpus ID: 89865053

Defining the anti-apoptotic function of the survival of motor neuron (SMN) protein and assessment of a novel therapy for the treatment of spinal muscular atrophy (SMA)

  title={Defining the anti-apoptotic function of the survival of motor neuron (SMN) protein and assessment of a novel therapy for the treatment of spinal muscular atrophy (SMA)},
  author={Ryan S. Anderton},
Spinal muscular atrophy (SMA) is a neurodegenerative disorder primarily affecting motor neurons. This untreatable disease is caused by the absence of a functional survival of motor neuron 1 (SMN1) gene, which leads to a critical reduction in fulllength survival of motor neuron (SMN) protein. The multifunctional SMN protein is important in the biogenesis of small nuclear ribonuclear proteins, pre-mRNA splicing and motor neuron viability. However, the precise functions of the SMN protein in… 

Survival motor neuron protein modulates neuron-specific apoptosis.

It is shown that SMN protects primary neurons and differentiated neuron-like stem cells, but not cultured cell lines from virus-induced apoptotic death, and increases survival of virus-infected mice.

Survival motor Neuron protein regulates apoptosis in anin vitro model of Spinal muscular atrophy

It is suggested not only that decreased smn levels increase apoptosis in an in vitro model of SMA, but also that increased smn can protect against neural injury.

The SMN complex.

The survival motor neuron protein in spinal muscular atrophy.

Investigation 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, which is consistent with features of this motor neuron disease.

Involvement of survival motor neuron (SMN) protein in cell death.

Results show that the C-terminal region is critical in suppression of apoptosis by SMN, indicating that its effects are through suppression of the mitochondrial apoptotic pathway.

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

Prolactin (PRL) treatment increased SMN levels, improved motor function, and enhanced survival in a mouse model of severe SMA, confirming earlier work suggesting STAT5 pathway activators as potential therapeutic compounds for the treatment of SMA and identifying PRL as one such promising agent.

Combination of SMN trans-splicing and a neurotrophic factor increases the life span and body mass in a severe model of spinal muscular atrophy.

Intracerebroventricular injection of the trans-splicing/IGF vector significantly increased SMN protein in brain and spinal cord of SMAΔ7 mice and lessened the severity of disease in a more severe mouse model as evidenced by an extension of life span and increased body mass.

A screen for regulators of survival of motor neuron protein levels.

An image-based screen of annotated chemical libraries was executed and it was particularly notable that GSK-3 chemical inhibitors were also effective in motor neurons, not only in elevating SMN levels, but also in blocking the death that was produced when SMN was acutely reduced by an SMN-specific shRNA.