Hyperphosphorylation and accumulation of neurofilament proteins in transgenic mice with Alzheimer presenilin 1 mutation.
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.
Yang
Xifei
X
Department of Pathophysiology, Institute of Neuroscience, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yang
Ying
Y
Luo
Yougen
Y
Li
Geng
G
Wang
Jianzhi
J
Yang
Edward S
ES
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism
D016900:Neurofilament Proteins; D053764:Presenilin-1; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases