Journal
NEUROBIOLOGY OF DISEASE
Volume 55, Issue -, Pages 129-139Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2013.03.004
Keywords
Alzheimer's disease; Soluble A beta oligomers; Synaptic vesicle trafficking; Phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P-2); Cyclin-dependent kinase 5 (CDK5)
Categories
Funding
- Korea Health Technology RD Project [A092058]
- Ministry of Health & Welfare, Republic of Korea
- Biomembrane Plasticity Research Center [20100029395]
- National Research Foundation of Korea
- Brain Research Center of the 21st Century Frontier Research Program [M103KV010009-06K2201-00910]
- Ministry of Education & Science & Technology, Republic of Korea
Ask authors/readers for more resources
Growing evidence supports a role for soluble amyloid-beta oligomer intermediates in the synaptic dysfunction associated with Alzheimer's disease (AD), but the molecular mechanisms underlying this effect remain unclear. We found that acute treatment of cultured rat hippocampal neurons with nanomolar concentrations of A beta oligomers reduced the recycling pool and increased the resting pool of synaptic vesicles. Endocytosis of synaptic vesicles and the regeneration of fusion-competent vesicles were also severely impaired. Furthermore, the release probability of the readily-releasable pool (RRP) was increased, and recovery of the RRP was delayed. All these effects were prevented by antibody against All. Moreover reduction of the pool size was prevented by inhibiting calpain or CDK5, while the defects in endocytosis were averted by overexpressing phosphatidylinositol-4-phosphate-5-kinase type I-gamma, indicating that these two downstream pathways are involved in,AS oligomers-induced presynaptic dysfunction. (c) 2013 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