Insulin receptor substrate protein p53 localization in rats suggests mechanism for specific polyglutamine neurodegeneration

被引:16
作者
Thomas, EA [1 ]
Foye, PE [1 ]
Alvarez, CE [1 ]
Usui, H [1 ]
Sutcliffe, JG [1 ]
机构
[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
关键词
insulin receptor substrate; dentatorubral-pallidoluysian atrophy; in situ hybridization; expression; striatum; cortex; neurodegeneration; polyglutamine;
D O I
10.1016/S0304-3940(01)02064-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dentatorubral-pallidoluysian atrophy (DRPLA) is a neurodegenerative disease that results from the expansion of an unstable CAG repeat within the coding regions of the DRPLA gene. Recently it was shown that the DRPLA gene product, atrophin-1, interacts with the human insulin receptor tyrosine kinase substrate protein, IRSp53. We have isolated rat and mouse cDNA clones for IRSp53 and determined expression patterns in rat central nervous system. In situ hybridization analysis revealed enriched IRSp53 mRNA expression in rat forebrain structures, including the cerebral cortex (layers II/III, V and VI), striatum, hippocampus and olfactory bulb. IRSp53 hybridization signals were also detected in the cerebellum, subthalamic nucleus, pons, amygdala and hypothalamus. These findings support the idea that insulin and insulin growth factor-1 have a role in neurotransmission, one that is regionally specific. The expression of IRSp53 in regions similar to those that degenerate in DRPLA supports the notion that IRSp53 is a relevant atrophin-1 binding protein and may provide a mechanism for region-specific neurodegeneration. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:145 / 148
页数:4
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