ID 111565
Author
Tamiya, Gen The University of Tokushima
Ando, Satoshi The University of Tokushima
Makino, Satoshi The University of Tokushima
Lee, LV Philippines National Children’s Medical Center
Keywords
dystonia
DYT3
striosome
dopamine
TAF1
Content Type
Journal Article
Description
Pathological findings in dystonia have been unclear. X-linked recessive dystonia-parkinsonism (XDP, DYT3), endemic in the Panay island, the Philippines, is characterized by the clinical onset with dystonia followed by parkinsonism. It provides a unique opportunity to explore the anatomical basis of dystonia, because it has discernible pathological changes even at its early phase of dystonia. After extensive searches for the anatomical basis in XDP, we found selective loss of striosomal neurons in the striatum in dystonic patients’ brain. Because striosomal neurons inhibit nigrostriatal dopaminergic neurons via GABAergic innervation, the striosomal lesion could account for dopamine excess in the striatum, which in turn causes a hyperkinetic state or dystonia. We also identified the causative gene as one of the general transcription factor genes, TAF1. XDP has certain similarities to Huntington disease not only in pathological and clinical findings, but also the molecular mechanism, which disturbs expression of genes essential for striatal neurons, such as DRD2. Therapeutic intervention may become possible through pharmacological measures that affect gene expression.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
AA12022913
Publisher
Faculty of Medicine Tokushima University
Volume
52
Issue
Supplement
Start Page
280
End Page
283
Sort Key
280
Published Date
2005-11
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Medical Sciences