Journal
LIFE SCIENCES
Volume 86, Issue 13-14, Pages 532-537Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2010.02.009
Keywords
Alzheimer's disease; Neurofilament; Tau; Axonal transport; Phosphorylation; Cyclin-dependent kinase 5
Funding
- National Natural Science Foundation of China [30570554, 30470348]
- Hubei Province Natural Science Foundation [2006S2153]
- Scientific and Technological Project in Hubei Province [2007AA3011331-2]
Ask authors/readers for more resources
Aims Alzheimer's disease (AD) is the leading cause of dementia The Increased cdk5 expression and enhanced phosphorylation of tau and NFs have been seen in AD patients Our study aimed at investigating the effects of increased cdk5 activity on axonal transport of neurofilaments (NFs). Main methods In this study, we used a molecular engineering approach to overexpress cdk5/p25 in neuroblastoma N2a cells and investigated the effects on axonal transport with live cell imaging techniques Key findings In stably transfected cells, there was a 2 5-fold increase in cdk5 activity compared to non-transfected cells, which in turn led to a dramatic increase in phosphorylation of NE's and tau at several phosphorylation sites Using time-lapse imaging technology, the transport of NFs was captured in the cells overexpressing cdk5/p25, which were also transiently transfected with fluorescence protein linked to the N-terminus of NF-M (EGFP-NFM) The cdk5/p25 cells displayed significantly slower rates of axonal transport of NFs, with accumulation of immobile NI; clusters observed in the cell body. Roscovitme, an inhibitor of cdk5, significantly reversed this defect in axonal transport. Significance These results suggest that increased cdk5 activity found in AD subjects may be crucially related to the pathogenesis of AD via an underlying mechanism by which it promotes accumulation of excessively phosphorylated cytoskeletal NF proteins, leading to the enduring impairment of axonal transport of NFs (C) 2010 Elsevier Inc. All rights reserved
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available