Widespread occurrence of intranuclear atrophin-1 accumulation in the central nervous system neurons of patients with dentatorubral-pallidoluysian atrophy
Corresponding Author
Mitsunori Yamada MD, PhD
Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
Department of Pathology, Brain Research Institute, Niigata University, 1 Asahimachi, Niigata 951-8585, JapanSearch for more papers by this authorJonathan D. Wood PhD
Department of Psychiatry and Behavioral Sciences, Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorTakayoshi Shimohata MD
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
Search for more papers by this authorShintaro Hayashi MD, PhD
Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
Search for more papers by this authorShoji Tsuji MD, PhD
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
Search for more papers by this authorChristopher A. Ross MD, PhD
Department of Psychiatry and Behavioral Sciences, Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD
Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorHitoshi Takahashi MD, PhD
Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
Search for more papers by this authorCorresponding Author
Mitsunori Yamada MD, PhD
Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
Department of Pathology, Brain Research Institute, Niigata University, 1 Asahimachi, Niigata 951-8585, JapanSearch for more papers by this authorJonathan D. Wood PhD
Department of Psychiatry and Behavioral Sciences, Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorTakayoshi Shimohata MD
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
Search for more papers by this authorShintaro Hayashi MD, PhD
Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
Search for more papers by this authorShoji Tsuji MD, PhD
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
Search for more papers by this authorChristopher A. Ross MD, PhD
Department of Psychiatry and Behavioral Sciences, Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD
Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorHitoshi Takahashi MD, PhD
Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
Search for more papers by this authorAbstract
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
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