Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Nov;22(11):1520-1530.
doi: 10.1038/mp.2017.171. Epub 2017 Sep 8.

Tau-mediated iron export prevents ferroptotic damage after ischemic stroke

Q-Z Tuo  1   2   3 , P Lei  2   3 , K A Jackman  2 , X-L Li  3 , H Xiong  3 , X-L Li  2   4 , Z-Y Liuyang  1 , L Roisman  5 , S-T Zhang  3 , S Ayton  2 , Q Wang  3 , P J Crouch  5 , K Ganio  2 , X-C Wang  1 , L Pei  6 , P A Adlard  2 , Y-M Lu  1 , R Cappai  5 , J-Z Wang  1 , R Liu  1 , A I Bush  2
Affiliations

Tau-mediated iron export prevents ferroptotic damage after ischemic stroke

Q-Z Tuo et al. Mol Psychiatry. 2017 Nov.

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 suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia-reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau-iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

LinkOut - more resources