报告题目: |
Neuronal iron is regulated by tau-mediated APP trafficking and its implications in Alzheimer’s disease and Parkinson’s disease |
报告人: |
Peng Lei |
|
Mental Health Research Institute, Australia
Department of Pathology, the University of Melbourne, Australia
|
报告时间: |
2011-09-14 10:00 |
报告地点: |
何添楼406会议室 |
主办单位: |
化学系 |
简介: |
摘 要：Iron accumulation was found in both Alzheimer's disease (AD) and Parkinson’s disease (PD). Until recently, we discovered β−amyloid protein precursor (APP) possesses a conserved H−ferritin−like ferroxidase domain, facilitates the efflux of iron from the cell via its transport to the cell surface where it interacts with the iron exporter, ferroportin1. Deletion of tau decreases mature APP on cell surface, causing an iron export lesion that resulted in an age−dependent neuronal iron accumulation paralleling studies with APP deficient cell cultures and brain tissue2. In tau KO mice, we found an age-dependent Parkinsonism with dementia phenotype which was prevented by oral treatment with a moderate iron chelator, clioquinol. We further found that APP transgenic mice were protected against neurodegeneration in the MPTP PD model. Coincident with iron elevation, both nigral tau and APP levels were decreased in both human cases and the mouse PD MPTP model. Collectively, these data indicate a new relationship between two characteristic proteins related to AD and how disruption in either or both functions can both lead to pro−oxidant neuronal Fe2+ elevation and contributes to neurodegenerative diseases such as AD and PD.
1. Duce, J. A. et al. Cell 142, 857-867 (2010).
2. Lei, P. et al. 40thAnnual Meeting of Neuroscience, San Diego, USA (2010).
|
|
