Journal article
Tau-mediated iron export prevents ferroptotic damage after ischemic stroke
QZ Tuo, P Lei, KA Jackman, XL Li, H Xiong, ZY Liuyang, L Roisman, ST Zhang, S Ayton, Q Wang, PJ Crouch, K Ganio, XC Wang, L Pei, PA Adlard, YM Lu, R Cappai, JZ Wang, R Liu, AI Bush
Molecular Psychiatry | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/mp.2017.171
Abstract
Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau su..
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Awarded by Australian Research Council
Funding Acknowledgements
We thank Drs Mian Bi, Lars Ittner and Brian Stevens for technical assistance, and Drs Geoffrey Donnan, David Howells and Craig Rosenfeld for critical review of the manuscript. This work was supported by funds from the Australian Research Council, the National Health and Medical Research Council of Australia (NHMRC), the Cooperative Research Center for Mental Health, Alzheimer's Australia Dementia Research Foundation, National Natural Science Foundation of China (81722016, 81571236, 81271403, 81471304, 91632115) and the Fundamental Research Funds for the Central Universities (2015XJGH013, 2017SCU12042). P Lei is supported by the Recruitment Program of Global Young Experts of China.