Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Burghes, Arthur H M; Beattie, Christine E
Year of Publication: 2009
Journal: Nat Rev Neurosci
Volume: 10
Issue: 8
Pagination: 597-609
Date Published: 2009 Aug
Publication Language: eng
ISSN: 1471-0048
Keywords: Humans, Models, Biological, Motor Neurons, Muscular Atrophy, Spinal, Ribonucleoproteins, Small Nuclear, Survival of Motor Neuron 1 Protein

Many neurogenetic disorders are caused by the mutation of ubiquitously expressed genes. One such disorder, spinal muscular atrophy, is caused by loss or mutation of the survival motor neuron1 gene (SMN1), leading to reduced SMN protein levels and a selective dysfunction of motor neurons. SMN, together with partner proteins, functions in the assembly of small nuclear ribonucleoproteins (snRNPs), which are important for pre-mRNA splicing. It has also been suggested that SMN might function in the assembly of other ribonucleoprotein complexes. Two hypotheses have been proposed to explain the molecular dysfunction that gives rise to spinal muscular atrophy (SMA) and its specificity to a particular group of neurons. The first hypothesis states that the loss of SMN's well-known function in snRNP assembly causes an alteration in the splicing of a specific gene (or genes). The second hypothesis proposes that SMN is crucial for the transport of mRNA in neurons and that disruption of this function results in SMA.

DOI: 10.1038/nrn2670
Alternate Journal: Nat. Rev. Neurosci.