Your browser doesn't support javascript.
loading
Prostaglandin A2 Interacts with Nurr1 and Ameliorates Behavioral Deficits in Parkinson's Disease Fly Model.
Rajan, Sreekanth; Toh, Hui Ting; Ye, Hong; Wang, Ziyin; Basil, Adeline Henry; Parnaik, Tanvi; Yoo, Jun Yeob; Lim, Kah-Leong; Yoon, Ho Sup.
Afiliación
  • Rajan S; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore. srajan@ntu.edu.sg.
  • Toh HT; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
  • Ye H; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
  • Wang Z; Neurodegeneration Research Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
  • Basil AH; Neurodegeneration Research Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
  • Parnaik T; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
  • Yoo JY; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
  • Lim KL; Neurodegeneration Research Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
  • Yoon HS; Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore, 308232, Singapore.
Neuromolecular Med ; 24(4): 469-478, 2022 12.
Article en En | MEDLINE | ID: mdl-35482177
The orphan nuclear receptor Nurr1 is critical for the development, maintenance, and protection of midbrain dopaminergic neurons. Recently, we demonstrated that prostaglandins E1 (PGE1) and PGA1 directly bind to the ligand-binding domain (LBD) of Nurr1 and stimulate its transcriptional activation function. In this direction, here we report the transcriptional activation of Nurr1 by PGA2, a dehydrated metabolite of PGE2, through physical binding ably supported by NMR titration and crystal structure. The co-crystal structure of Nurr1-LBD bound to PGA2 revealed the covalent coupling of PGA2 with Nurr1-LBD through Cys566. PGA2 binding also induces a 21° shift of the activation function 2 (AF-2) helix H12 away from the protein core, similar to that observed in the Nurr1-LBD-PGA1 complex. We also show that PGA2 can rescue the locomotor deficits and neuronal degeneration in LRRK2 G2019S transgenic fly models.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Prostaglandinas A / Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Neuromolecular Med Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Prostaglandinas A / Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Neuromolecular Med Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos