Downregulation of astrocytic C3 production alleviates neuronal mitochondrial dysfunction in tauopathy models

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 14, 2024

Abstract Neuronal mitochondrial dysfunction is associated with cognitive decline in neurodegenerative disorders such as Alzheimer’s Disease (AD). In this study, multiple pieces of evidence proved that phosphorylated tau (p-Tau) caused swelling and neurons. a novel vitro newborn neurons culture system, we discovered were increased p-Tau, leading to necroptosis activation, which was induced by Complement C3 (C3) produced from activated astrocytes. the vivo tauopathy mouse models, effects astrocytic on tau-associated also hippocampal neurons, directly showed p-Tau aggregation mitochondria electron microscopy analysis. addition, ability compound anserine, can block Tak1-Ikk dependent NF-κB further down-regulate production alleviate neuronal , respectively. Down-regulation astrocyte C3-production anserine could rescue mortality well motor functions. Our findings first reported contribution proposed therapies have potential role alleviating neurotoxic effect.

Язык: Английский

散发性早发型阿尔茨海默病：独特特征、关键机制与未来展望

Chinese Science Bulletin (Chinese Version), Год журнала: 2024, Номер 70(1), С. 6 - 7

Опубликована: Ноя. 29, 2024

Targeted protein degradation with bifunctional molecules as a novel therapeutic modality for Alzheimer's disease & beyond

Neurotherapeutics, Год журнала: 2024, Номер unknown, С. e00499 - e00499

Опубликована: Дек. 1, 2024

Язык: Английский