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NLRP3 Inflammasome Inhibitor Ameliorates Amyloid Pathology in a Mouse Model of Alzheimer's Disease.
Yin, Jun; Zhao, Fanpeng; Chojnacki, Jeremy E; Fulp, Jacob; Klein, William L; Zhang, Shijun; Zhu, Xiongwei.
Afiliación
  • Yin J; Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
  • Zhao F; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
  • Chojnacki JE; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
  • Fulp J; Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, 23298, USA.
  • Klein WL; Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, 23298, USA.
  • Zhang S; Department of Neurobiology, Northwestern University, Evanston, IL, USA.
  • Zhu X; Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, 23298, USA. szhang2@vcu.edu.
Mol Neurobiol ; 55(3): 1977-1987, 2018 03.
Article en En | MEDLINE | ID: mdl-28255908
The activation of the NLRP3 inflammasome signaling pathway plays an important role in the neuroinflammation in Alzheimer's disease (AD). In this study, we investigated the effects of JC-124, a rationally designed NLRP3 inflammasome inhibitor, on AD-related deficits in CRND8 APP transgenic mice (TgCRND8). We first demonstrated increased formation and activation of NLRP3 inflammasome in TgCRND8 mice compared to non-transgenic littermate controls, which was inhibited by the treatment with JC-124. Importantly, JC-124 treatment led to decreased levels of Aß deposition and decreased levels of soluble and insoluble Aß1-42 in the brain of CRND8 mice which was accompanied by reduced ß-cleavage of APP, reduced activation of microglia but enhanced astrocytosis. Oxidative stress was decreased and synaptophysin was increased in the CRND8 mice after JC-124 treatment, demonstrating a neuroprotective effect. Overall, these data demonstrated beneficial effects of JC-124 as a specific NLRP3 inflammasome inhibitor in AD mouse model and supported the further development of NLRP3 inflammasome inhibitors as a viable option for AD therapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Proteína con Dominio Pirina 3 de la Familia NLR / Amiloide Límite: Animals Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2018 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: Enfermedad de Alzheimer / Proteína con Dominio Pirina 3 de la Familia NLR / Amiloide Límite: Animals Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos