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Widespread occurrence of intranuclear atrophin‐1 accumulation in the central nervous system neurons of patients with dentatorubral‐pallidoluysian atrophy
Author(s) -
Yamada Mitsunori,
Wood Jonathan D.,
Shimohata Takayoshi,
Hayashi Shintaro,
Tsuji Shoji,
Ross Christopher A.,
Takahashi Hitoshi
Publication year - 2001
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(200101)49:1<14::aid-ana5>3.0.co;2-x
Subject(s) - central nervous system , biology , atrophy , pathology , lesion , trinucleotide repeat expansion , promyelocytic leukemia protein , nuclear protein , neuroscience , medicine , transcription factor , genetics , allele , gene
Dentatorubral‐pallidoluysian 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. Ann Neurol 2001;49:14–23