Mutant huntingtin induces iron overload via up-regulating IRP1 in Huntington's disease

作者：Niu, Li; Ye, Cuifang^*; Sun, Yun; Peng, Ting; Yang, Miming; Wang, Weixi; Li, He^*

来源：Cell and Bioscience, 2018, 8(1): 41.

DOI：10.1186/s13578-018-0239-x

• Huntington's disease
• Iron
• Iron response protein 1
• Transferrin receptor
• Transferrin
• Ferritin

Background: Iron accumulation in basal ganglia accompanies neuronal loss in Huntington's disease (HD) patients and mouse disease models Disruption of HD brain iron homeostasis occurs before the onset of clinical signs. Therefore, investigating the mechanism of iron accumulation is essential to understanding its role in disease pathogenesis. @@@ Methods: N171-82Q HD transgenic mice brain iron was detected by using Diaminobenzidine-enhanced Perls'stain. Iron homeostatic proteins including iron response protein 1 (IRP1), transferrin (Tf), ferritin and transferrin receptor (TfR) were determined by using western blotting and immunohistochemistry, and their relative expression levels of RNA were measured by RT-PCR in both N171-82Q HD transgenic mice and HEK293 cells expressing N-terminal of huntingtin. @@@ Results: Iron was increased in striatum and cortex of N171-82Q HD transgenic mice. Analysis of iron homeostatic proteins revealed increased expression of IRP1, Tf, ferritin and TfR in N171-82Q mice striatum and cortex. The same results were obtained in HEK293 cells expressing N-terminal of mutant huntingtin containing 160 CAG repeats. @@@ Conclusion: We conclude that mutant huntingtin may cause abnormal iron homeostatic pathways by increasing IRP1 expression in Huntington's disease, suggesting potential therapeutic target.

• 出版日期2018-7-4
• 单位华中科技大学