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Spinal muscular atrophy (SMA) is a heterogeneous group of neuromuscular disorders caused by degeneration of lower motor neurons. Although functional loss of SMN1 is associated with autosomal-recessive childhood SMA, the genetic cause for most families affected by dominantly inherited SMA is unknown. Here, we identified pathogenic variants in bicaudal D(More)
Among a panel of histone deacetylase (HDAC) inhibitors investigated, suberoylanilide hydroxamic acid (SAHA) evolved as a potent and non-toxic candidate drug for the treatment of spinal muscular atrophy (SMA), an alpha-motoneurone disorder caused by insufficient survival motor neuron (SMN) protein levels. SAHA increased SMN levels at low micromolar(More)
Applying the recently developed DNA array technique to a murine stroke model, we found that the gene coding for RhoB, a member of the family of GTPases that regulate a variety of signal transduction pathways, is upregulated in ischemia-damaged neurons. RhoB immunoreactivity precedes DNA single-strand breaks and heralds the evolving infarct, making it an(More)
Histone deacetylase inhibitors (HDACi) are potential candidates for therapeutic approaches in cancer and neurodegenerative diseases such as spinal muscular atrophy (SMA)--a common autosomal recessive disorder and frequent cause of early childhood death. SMA is caused by homozygous absence of SMN1. Importantly, all SMA patients carry a nearly identical copy(More)
Several lines of evidence demonstrate that the DNA of the iridovirus frog virus 3 (FV3) is methylated in all 5'-CG-3' sequences both in virion DNA and in the intracellular viral DNA at late times after infection. The 5-methyldeoxycytidine residues in this viral DNA occur exclusively in 5'-CG-3' dinucleotide positions. We have cloned and determined the(More)
Homozygous SMN1 loss causes spinal muscular atrophy (SMA), the most common lethal genetic childhood motor neuron disease. SMN1 encodes SMN, a ubiquitous housekeeping protein, which makes the primarily motor neuron-specific phenotype rather unexpected. SMA-affected individuals harbor low SMN expression from one to six SMN2 copies, which is insufficient to(More)
Spinal muscular atrophy (SMA) is a devastating motoneuron (MN) disorder caused by homozygous loss of SMN1. Rarely, SMN1-deleted individuals are fully asymptomatic despite carrying identical SMN2 copies as their SMA III-affected siblings suggesting protection by genetic modifiers other than SMN2. High plastin 3 (PLS3) expression has previously been found in(More)
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