Hyperphosphorylation and Accumulation of Neurofilament Proteins in Transgenic Mice with Alzheimer Presenilin 1 Mutation

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• 作者：Xifei Yang ; Ying Yang ; Yougen Luo ; Geng Li ; Jianzhi Wang and Edward S. Yang
• 关键词：Neurofilaments ; Hyperphosphorylation ; JNK ; Presenilin ; 1 ; Alzheimer’ ; s disease
• 刊名：Cellular and Molecular Neurobiology
• 出版年：2009
• 出版时间：June, 2009
• 年：2009
• 卷：29
• 期：4
• 页码：497-501
• 全文大小：266.4 KB

文摘

Neurofilaments (NFs) are hyperphosphorylated and accumulate in Alzheimer’s disease (AD) brains. In this study, employing the transgenic mouse model, we explored the effect of presenilin 1 (PS-1) mutation on the phosphorylation and distribution of NFs. Western blot analysis showed that there was a significant increase in the phosphorylation of NF-H and NF-M subunits with a concomitant increase in phosphorylated c-Jun N-terminal protein kinase 1/2 (JNK1/2) mitogen-activated protein kinase (MAPK) in hippocampus of PS-1 transgenic mice compared to that of wild-type littermates. Immunohistochemical analysis revealed that phosphorylated NFs accumulated throughout the hippocampal neurons of the transgenic mice. These findings suggest that PS-1 mutation may induce hyperphosphorylation and accumulation of NFs via a JNK1/2-involved mechanism.