Abstract
Degenerated motor neurons in the spinal cord are the pathological hallmark of spinal muscular atrophy (SMA). SMA is caused by mutations in the ubiquitously expressed survival motor neuron 1 (SMN1) gene, which lead to reduced levels of functional SMN protein. Many different functions have been assigned to SMN, including assembly of ribonucleoproteins (RNPs), splicing, transcription and axonal mRNA transport. Recently, tissue from SMA patients and animal models has been used to determine which function of SMN is affected in SMA patients. A surprising picture has emerged: the impaired assembly of RNP subunits of the spliceosome seems to be responsible for SMA pathogenesis. Here, we present a model of how this defect might cause motor-neuron degeneration and consider potential therapies.
MeSH terms
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Alternative Splicing
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Animals
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Cyclic AMP Response Element-Binding Protein* / genetics
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Cyclic AMP Response Element-Binding Protein* / metabolism
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Humans
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Motor Neurons / cytology
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Motor Neurons / metabolism
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Motor Neurons / pathology
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Muscular Atrophy, Spinal* / genetics
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Muscular Atrophy, Spinal* / pathology
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Muscular Atrophy, Spinal* / physiopathology
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Muscular Atrophy, Spinal* / therapy
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Nerve Tissue Proteins* / genetics
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Nerve Tissue Proteins* / metabolism
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RNA, Messenger / metabolism
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RNA-Binding Proteins* / genetics
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RNA-Binding Proteins* / metabolism
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Ribonucleoproteins / genetics
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Ribonucleoproteins / metabolism*
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SMN Complex Proteins
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Survival of Motor Neuron 1 Protein
Substances
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Cyclic AMP Response Element-Binding Protein
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Nerve Tissue Proteins
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RNA, Messenger
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RNA-Binding Proteins
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Ribonucleoproteins
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SMN Complex Proteins
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SMN1 protein, human
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Survival of Motor Neuron 1 Protein