Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dystonia musculorum (dt) is a mutant mouse with hereditary sensory neuropathy. A defective bullous pemphigoid antigen 1 (BPAG1) gene is responsible for this mutation. In the present study, we examined the distribution of neuronal intermediate filament proteins in the central and peripheral processes of the dorsal root ganglia (DRG) in adult dt mice using different approaches. We found that not only BPAG1, but also alpha-internexin was absent in the DRG neurons in adult dt mice. To study the relationship between the absence of alpha-internexin and the progressive neuronal loss in the DRG of dt mice, we further cultured DRG neurons from embryonic dt mutants. Immunocytochemical assay of cultured DRG neurons from dt embryos revealed that alpha-internexin was aggregated in the proximal region of axons and juxtanuclear region of the cytoplasma, yet the other intermediate filament proteins were widely distributed in all processes. The active caspase-3 activity was observed in the dt neuron with massive accumulation of alpha-internexin. From our observations, we suggest that the interaction between BPAG1 and alpha-internexin may be one of the key factors involved in neuronal degeneration, and abnormal accumulation of alpha-internexin may impair the axonal transport and subsequently turns on the cascade of neuronal apoptosis in dt mice.
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PMID:A possible cellular mechanism of neuronal loss in the dorsal root ganglia of Dystonia musculorum (dt) mice. 1735 86

Dystonia musculorum (dt) is a mutant mouse with hereditary neuropathy where the dysfunction is mainly found in the dorsal root ganglia (DRG) neurons but not in the spinal motor neurons. However, the accumulation of intermediate filament (IF) proteins in the swelling axons of spinal motor neurons could be found in dt/dt mice. In order to understand the pathological role of neuronal IFs in the swelling axons of spinal motor neurons from dt/dt mice, we extensively examined the distribution of neuronal IF proteins. By immunofluorescence staining, our results indicated that alpha-internexin was a major component in the swelling axon and showed abnormal translocation in the nuclei of spinal motor neurons in dt/dt mice. This abnormal translocation of alpha-internexin in the nuclei of spinal motor neurons was also confirmed by Western blotting and immunoelectron microscopy. Instead of the 10-nm filamentous structure, a diffuse immunopositive pattern of alpha-internexin was observed in the nucleus of spinal motor neurons in dt/dt mutants. We further examined the cell death of spinal motor neurons by TUNEL assay, and no TUNEL-positive cells could be identified from spinal motor neurons in dt/dt mice. From these observations we suggest that abnormal accumulation of neuronal IFs in the swelling axons and abnormal translocation of alpha-internexin in the nuclei of the spinal motor neurons from dt/dt mice may not directly cause cell death of the spinal motor neurons.
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PMID:Abnormal cellular translocation of alpha-internexin in spinal motor neurons of Dystonia musculorum mice. 1809 35