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Chronic stress induces Alzheimer's disease-like pathologies through DNA damage-Chk1-CIP2A signaling.
Wang, Zhuoqun; Zhang, Lun; Yang, Jiayu; Zeng, Yi; Su, Chengke; Yao, Mengdong; Zhang, Huiliang; Hu, Wenting; Liu, Yi; Lai, Yiwen; Wang, Xiaochuan; Zeng, Ji; Liu, Rong.
Afiliación
  • Wang Z; Department of Pathophysiology, Key Laboratory of Ministry of Education/Hubei Province for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Zhang L; Department of Pathophysiology, Key Laboratory of Ministry of Education/Hubei Province for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Yang J; Department of Clinical Laboratory, Wuhan Fourth Hospital, Wuhan, China.
  • Zeng Y; Department of Pathophysiology, Key Laboratory of Ministry of Education/Hubei Province for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Su C; Department of Pathophysiology, Key Laboratory of Ministry of Education/Hubei Province for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Yao M; Department of Pathophysiology, Key Laboratory of Ministry of Education/Hubei Province for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Zhang H; Department of Pathophysiology, Key Laboratory of Ministry of Education/Hubei Province for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Hu W; Department of Pathophysiology, Key Laboratory of Ministry of Education/Hubei Province for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Liu Y; Department of Pathophysiology, Key Laboratory of Ministry of Education/Hubei Province for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Lai Y; Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, China.
  • Wang X; Department of Pathophysiology, Key Laboratory of Ministry of Education/Hubei Province for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Zeng J; Department of Pathophysiology, Key Laboratory of Ministry of Education/Hubei Province for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Liu R; Department of Pathophysiology, Key Laboratory of Ministry of Education/Hubei Province for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Aging (Albany NY) ; 16(10): 9168-9187, 2024 05 30.
Article en En | MEDLINE | ID: mdl-38819231
ABSTRACT
Stress is an important initiating factor in promoting Alzheimer's disease (AD) pathogenesis. However, the mechanism by which stress induces AD-like cognitive impairment remains to be clarified. Here, we demonstrate that DNA damage is increased in stress hormone Corticotropin-releasing factor (CRF)-treated cells and in brains of mice exposed to chronic restraint stress. Accumulation of DNA damage drives activation of cell cycle checkpoint protein kinase 1 (Chk1), upregulation of cancerous inhibitor of PP2A (CIP2A), tau hyperphosphorylation, and Aß overproduction, eventually resulting in synaptic impairment and cognitive deficits. Pharmacological intervention targeting Chk1 by specific inhibitor and DNA damage by vitamin C, suppress DNA damage-Chk1-CIP2A signaling pathway in chronic stress animal model, which in turn attenuate AD-like pathologies, synaptic impairments and cognitive deficits. Our study uncovers a novel molecular mechanism of stress-induced AD-like pathologies and provides effective preventive and therapeutic strategies targeting this signaling pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Psicológico / Daño del ADN / Transducción de Señal / Enfermedad de Alzheimer / Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) Límite: Animals Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Psicológico / Daño del ADN / Transducción de Señal / Enfermedad de Alzheimer / Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) Límite: Animals Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos