TorsinA protein and neuropathology in early onset generalized dystonia with GAG deletion

Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. Most cases are caused by a 3-bp deletion (GAG) in the coding region of the TOR1A ( DYT1) gene, which is widely expressed in human brain and encodes the protein torsinA. This study compares neuropathol...

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Veröffentlicht in:Neurobiology of disease Jg. 12; H. 1; S. 11 - 24
Hauptverfasser: Rostasy, Kevin, Augood, Sarah J, Hewett, Jeffrey W, Leung, Joanne Chung-on, Sasaki, Hikaru, Ozelius, Laurie J, Ramesh, Vijaya, Standaert, David G, Breakefield, Xandra O, Hedreen, John C
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Elsevier Inc 01.02.2003
Elsevier
Schlagworte:
Adolescent
Adult
Aged
Brain - metabolism
Brain - pathology
Brain - physiopathology
Carrier Proteins - genetics
Carrier Proteins - metabolism
Dystonia
Dystonia Musculorum Deformans - genetics
Dystonia Musculorum Deformans - metabolism
Dystonia Musculorum Deformans - pathology
Female
Gene Deletion
Genotype
Human brain
Humans
Immunohistochemistry
Infant
Male
Middle Aged
Molecular Chaperones
Mutation - genetics
Neurons - metabolism
Neurons - pathology
Substantia nigra
Torsin
Human brain
Torsin
Dystonia
Substantia nigra
ISSN:0969-9961, 1095-953X
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Zusammenfassung:Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. Most cases are caused by a 3-bp deletion (GAG) in the coding region of the TOR1A ( DYT1) gene, which is widely expressed in human brain and encodes the protein torsinA. This study compares neuropathology and torsinA expression in the normal human brain with that in dystonia cases with and without the GAG deletion. TorsinA-like protein was expressed in neuronal cytoplasm throughout the human brain, including cerebellum, substantia nigra, hippocampus, and neostriatum, with higher levels in specific neurons. This immunostaining pattern was not discernibly different in dystonia and normal brains in midbrain and neostriatal regions. However, nigral dopaminergic neurons appeared to be larger in both GAG-deletion and non-GAG-deletion dystonia brains compared to normal, and may be more closely spaced in GAG-deletion brains. Beyond these apparent changes in neuronal size and spacing in dystonia brains, there was no indication of neuron loss, inflammation, DNA strand breaks, or altered distribution of torsin-like immunoreactivity, supporting a functional rather than degenerative etiology of early onset torsion dystonia.
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ISSN:0969-9961
1095-953X
DOI:10.1016/S0969-9961(02)00010-4