RGD Reference Report - Tau-mediated iron export prevents ferroptotic damage after ischemic stroke. - Rat Genome Database
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Tau-mediated iron export prevents ferroptotic damage after ischemic stroke.

Authors: Tuo, Q-Z  Lei, P  Jackman, K A  Li, X-L  Xiong, H  Li, X-L  Liuyang, Z-Y  Roisman, L  Zhang, S-T  Ayton, S  Wang, Q  Crouch, P J  Ganio, K  Wang, X-C  Pei, L  Adlard, P A  Lu, Y-M  Cappai, R  Wang, J-Z  Liu, R  Bush, A I 
Citation: Tuo QZ, etal., Mol Psychiatry. 2017 Nov;22(11):1520-1530. doi: 10.1038/mp.2017.171. Epub 2017 Sep 8.
RGD ID: 13800886
Pubmed: (View Article at PubMed) PMID:28886009
DOI: Full-text: DOI:10.1038/mp.2017.171

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.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Mapt  (microtubule-associated protein tau)

Genes (Mus musculus)
Mapt  (microtubule-associated protein tau)

Genes (Homo sapiens)
MAPT  (microtubule associated protein tau)


Additional Information