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

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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.

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Abbreviations

AD:

Alzheimer’s disease

PS-1:

Presenilin 1

NF:

Neurofilament

JNK1/2:

c-Jun N-terminal protein kinase 1/2

ERK1/2:

Extracellular signal-regulated kinases 1/2

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Acknowledgment

This study was supported by a grant from National Natural Science Foundation of China (30700277).

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Correspondence to Geng Li.

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Yang, X., Yang, Y., Luo, Y. et al. Hyperphosphorylation and Accumulation of Neurofilament Proteins in Transgenic Mice with Alzheimer Presenilin 1 Mutation. Cell Mol Neurobiol 29, 497–501 (2009). https://doi.org/10.1007/s10571-008-9341-7

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  • DOI: https://doi.org/10.1007/s10571-008-9341-7

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