The yeast protein Ure2p triggers Tau pathology in a mouse model of tauopathy
Lanxia Meng,
Congcong Liu,
Miao Liu,
Jiehui Chen,
Chaoyang Liu,
Zhaohui Zhang,
Guiqin Chen,
Zhentao Zhang
Affiliations
Lanxia Meng
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Congcong Liu
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Miao Liu
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Jiehui Chen
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Chaoyang Liu
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan 430073, China
Zhaohui Zhang
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Guiqin Chen
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
Zhentao Zhang
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China; TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430000, China; Corresponding author
Summary: The molecular mechanisms that trigger Tau aggregation in Alzheimer’s disease (AD) remain elusive. Fungi, especially Saccharomyces cerevisiae (S. cerevisiae), can be found in brain samples from patients with AD. Here, we show that the yeast protein Ure2p from S. cerevisiae interacts with Tau and facilitates its aggregation. The Ure2p-seeded Tau fibrils are more potent in seeding Tau and causing neurotoxicity in vitro. When injected into the hippocampus of Tau P301S transgenic mice, the Ure2p-seeded Tau fibrils show enhanced seeding activity compared with pure Tau fibrils. Strikingly, intracranial injection of Ure2p fibrils promotes the aggregation of Tau and cognitive impairment in Tau P301S mice. Furthermore, intranasal infection of S. cerevisiae in the nasal cavity of Tau P301S mice accelerates the aggregation of Tau. Together, these observations indicate that the yeast protein Ure2p initiates Tau pathology. Our results provide a conceptual advance that non-mammalian prions may cross-seed mammalian prion-like proteins.
