Abstract
Background and ObjectiveThere is circumstantial evidence linking sporadic amyotrophic lateral sclerosis (ALS) cases to a malfunction or deficit of a multimeric SMN complex that scrutinizes cellular RNAs; the core of this complex is survival motor neuron (SMN, or gemin 1) protein. We intended to verify this hypothesis by comparing the expression of both SMN and several other functionally associated gemins in the anterior horn motoneurons of patients who died of sporadic ALS (sALS), of transgenic rats with overexpression of the mutated human superoxide dismutase 1 gene (SOD1G93A) that represent a model of familial ALS (fALS), and of the respective controls.MethodsUsing archival material of paraffin blocks with samples of human and rat spinal cords, immunohistochemical reactions with antibodies against SMN and gemins 2, 3, and 4 were performed and assessed by light microscopy.ResultsThe expression of SMN and all other studied gemins was observed in motoneurons of sALS patients, fALS rats, and in all controls, although the intensity varied. The immunolabeling was most intense in sALS patients with relatively fast disease course, and decreased with increasing disease duration in both the human sALS and rat fALS material. Irrespective of the disease stage, sALS material showed no or very low gemin 2 immunoreactivity, while clear gemin 2 immnoreactivity was observed in all fALS rats and control material.ConclusionThe deficient expression of gemin 2 in spinal cord motoneurons in human sALS may lead to a dysfunction and loss of neuroprotective action of the SMN complex.
Highlights
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of mostly unknown etiology
In the human control material, both survival motor neuron (SMN) and all investigated gemins were detected in spinal cord motoneurons and interneurons
In amyotrophic lateral sclerosis (ALS), both anterior horn motoneurons and interneurons showed the expression of SMN and gemin 3 in all human spinal cord samples
Summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of mostly unknown etiology. Sporadic (sALS) and familial (fALS) forms of the disease represent about 90% and 10% of all ALS cases, respectively. The core of the SMN complex is survival motor neuron (SMN) protein that is functionally associated with gemins (for review see [2]). There is circumstantial evidence linking sporadic amyotrophic lateral sclerosis (ALS) cases to a malfunction or deficit of a multimeric SMN complex that scrutinizes cellular RNAs; the core of this complex is survival motor neuron (SMN, or gemin 1) protein. We intended to verify this hypothesis by comparing the expression of both SMN and several other functionally associated gemins in the anterior horn motoneurons of patients who died of sporadic ALS (sALS), of transgenic rats with overexpression of the mutated human superoxide dismutase 1 gene (SOD1G93A) that represent a model of familial ALS (fALS), and of the respective controls
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