301. Hyperphosphorylation and accumulation of neurofilament proteins in transgenic mice with Alzheimer presenilin 1 mutation.
- Author
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Yang X, Yang Y, Luo Y, Li G, Wang J, and Yang ES
- Subjects
- Alzheimer Disease metabolism, Animals, Disease Models, Animal, Extracellular Signal-Regulated MAP Kinases metabolism, Hippocampus cytology, Hippocampus metabolism, JNK Mitogen-Activated Protein Kinases metabolism, Male, Mice, Neurofilament Proteins genetics, Phosphorylation, Presenilin-1 metabolism, Alzheimer Disease genetics, Mice, Transgenic, Neurofilament Proteins metabolism, Presenilin-1 genetics
- Abstract
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.
- Published
- 2009
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