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- W2976666431 abstract "Abstract Impaired proteostasis has been linked to various diseases, whereas little is known about the impact of peripherally misfolded proteins on the brain. We here studied the brain of mice with cardiomyocyte-restricted overexpression of a missense (R120G) mutant small heat shock protein, αB-crystallin (CryAB R120G ). At baseline, the CryAB R120G mice showed impaired cognitive and motor functions, aberrant protein aggregates, neuroinflammation, impaired blood-brain barrier, and reduced proteasome activity in the brain compared with their non-transgenic (Ntg) littermates. Ischemic stroke dramatically exacerbated these pathological alterations and caused more severe brain dysfunction in CryAB R120G mice than in the Ntg mice. Intravenously injecting the exosomes isolated from CryAB R120G mouse blood into wild-type mice caused the similar phenotypes seen from CryAB R120G mice. Importantly, the CryAB R120G protein showed the prion-like properties. These results suggest that peripherally misfolded proteins in the heart remotely disrupt brain function through prion-like neuropathology, which may represent an underappreciated mechanism underlying heart-brain crosstalk." @default.
- W2976666431 created "2019-10-03" @default.
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- W2976666431 date "2019-09-30" @default.
- W2976666431 modified "2023-09-23" @default.
- W2976666431 title "Peripherally expressed misfolded proteins remotely disrupt brain function and aggravate stroke-induced brain injury" @default.
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- W2976666431 doi "https://doi.org/10.1101/785477" @default.
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