Spinal muscular atrophy.
Spinal muscular atrophies (SMA) are frequent autosomal recessive disorders characterized by degeneration of lower motor neurons. SMA are caused by mutations of the survival of motor neuron gene (SMN1) leading to a reduction of the SMN protein amount. The identification of SMN interacting proteins involved in the formation of the spliceosome and splicing changes in SMN-deficient tissues of mutant mice strongly support the view that SMN is involved in the splicing reaction. However, the molecular pathway linking SMN defect to the SMA phenotype remains unclear. From a better knowledge of the genetic basis of SMA and the defects resulting from the mutations of SMN1 in cellular or animal models, several therapeutics strategies have been selected aiming at targeting SMN2, a partially functional copy of SMN1 gene which remains present in patients, or to prevent neurons from death. Refined characterization of the degenerative process in SMA and the identification of the defective molecular pathway downstream from the SMN defect will provide further exciting insight into this disease in the near future. They should contribute to clarify the pathophysiology of SMA, the function of SMN and should help in designing potential targeted or non-targeted therapeutic molecules.
Vitte
Jérémie
J
Department of Human Genetics, Hadassah University Hospital, PO Box 91120, Jerusalem, Israel.
Attali
Ruben
R
Warwar
Nasim
N
Gurt
Irena
I
Melki
Judith
J
D000818:Animals; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D055532:SMN Complex Proteins / Q000235:genetics / Q000378:metabolism
D055532:SMN Complex Proteins