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PMID: 19343312 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Spinal muscular atrophy and a model for survival of motor neuron protein function in axonal ribonucleoprotein complexes.

Results and problems in cell differentiation ·Vol. 48 ·2009-00-00 ·Pages 289-326

Rossoll W, Bassell GJ

Abstract

Spinal muscular atrophy (SMA) is a neurodegenerative disease that results from loss of function of the SMN1 gene, encoding the ubiquitously expressed survival of motor neuron (SMN) protein, a protein best known for its housekeeping role in the SMN-Gemin multiprotein complex involved in spliceosomal small nuclear ribonucleoprotein (snRNP) assembly. However, numerous studies reveal that SMN has many interaction partners, including mRNA binding proteins and actin regulators, suggesting its diverse role as a molecular chaperone involved in mRNA metabolism. This review focuses on studies suggesting an important role of SMN in regulating the assembly, localization, or stability of axonal messenger ribonucleoprotein (mRNP) complexes. Various animal models for SMA are discussed, and phenotypes described that indicate a predominant function for SMN in neuronal development and synapse formation. These models have begun to be used to test different therapeutic strategies that have the potential to restore SMN function. Further work to elucidate SMN mechanisms within motor neurons and other cell types involved in neuromuscular circuitry hold promise for the potential treatment of SMA.

MeSH Terms
Actins/metabolism Animals Axons/physiology Caenorhabditis elegans Disease Models, Animal Drosophila Humans Mice Models, Biological Muscular Atrophy, Spinal/genetics,therapy RNA, Messenger/metabolism SMN Complex Proteins/genetics,physiology Survival of Motor Neuron 1 Protein/genetics,physiology Zebrafish
Chemicals
Actins RNA, Messenger SMN Complex Proteins Survival of Motor Neuron 1 Protein
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Rossoll Wilfried
Departments of Cell Biology and Neurology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA. [email protected]
Bassell Gary J
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Article Info
Journal
Results and problems in cell differentiation
Abbr.
Results Probl Cell Differ
ISSN
0080-1844
DOI
10.1007/400_2009_4
Email
[email protected]
Published
2009-00-00
Pages
289-326
Language
English
Region
Germany
NLM ID
0173555
PMCID
PMC3718852
Subset
IM
Grants
NICHD NIH HHS · R01 HD055835 · United States
NICHD NIH HHS · R21 HD056130 · United States
NICHD NIH HHS · HD56130 · United States
NICHD NIH HHS · HD055835 · United States
External Links
PubMed source DOI: 10.1007/400_2009_4 PMC Full Text
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