TY - JOUR
T1 - Widespread occurrence of intranuclear atrophin-1 accumulation in the central nervous system neurons of patients with dentatorubral-pallidoluysian atrophy
AU - Yamada, Mitsunori
AU - Wood, Jonathan D.
AU - Shimohata, Takayoshi
AU - Hayashi, Shintaro
AU - Tsuji, Shoji
AU - Ross, Christopher A.
AU - Takahashi, Hitoshi
PY - 2001
Y1 - 2001
N2 - Dentatorubral-pallidoluyslan atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion. In the present study of DRPLA, we have demonstrated immunohistochemically that diffuse accumulation of mutant atrophin-1 in the neuronal nuclei, rather than the formation of neuronal intranuclear inclusions (NIIs), was the predominant pathologic condition and involved a wide range of central nervous system regions far beyond the systems previously reported to be affected. In the neuronal nuclei harboring NIIs, promyelocytic leukemia protein (PML) nuclear bodies were redistributed into a single NII, and the CREB (cAMP-responsive element-binding protein)-binding protein was also recruited into NIIs. The results suggest that the novel lesion distribution revealed by the diffuse nuclear labeling may be responsible for a variety of clinical features, such as dementia and epilepsy in DRPLA, and that certain transcriptional abnormalities may be induced secondarily in neuronal nuclei with the formation of NIIs.
AB - Dentatorubral-pallidoluyslan atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion. In the present study of DRPLA, we have demonstrated immunohistochemically that diffuse accumulation of mutant atrophin-1 in the neuronal nuclei, rather than the formation of neuronal intranuclear inclusions (NIIs), was the predominant pathologic condition and involved a wide range of central nervous system regions far beyond the systems previously reported to be affected. In the neuronal nuclei harboring NIIs, promyelocytic leukemia protein (PML) nuclear bodies were redistributed into a single NII, and the CREB (cAMP-responsive element-binding protein)-binding protein was also recruited into NIIs. The results suggest that the novel lesion distribution revealed by the diffuse nuclear labeling may be responsible for a variety of clinical features, such as dementia and epilepsy in DRPLA, and that certain transcriptional abnormalities may be induced secondarily in neuronal nuclei with the formation of NIIs.
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U2 - 10.1002/1531-8249(200101)49:1<14::AID-ANA5>3.0.CO;2-X
DO - 10.1002/1531-8249(200101)49:1<14::AID-ANA5>3.0.CO;2-X
M3 - Article
C2 - 11198291
AN - SCOPUS:0035112686
SN - 0364-5134
VL - 49
SP - 14
EP - 23
JO - Annals of neurology
JF - Annals of neurology
IS - 1
ER -