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Astroglial membrane camouflaged Ptbp1 siRNA delivery hinders glutamate homeostasis via SDH/Nrf2 pathway.
Liu, Yan; Ren, Jian; Zhang, Wenlong; Ding, Liuyan; Ma, Runfang; Zhang, Mengran; Zheng, Shaohui; Liang, Ruijing; Zhang, Yunlong.
Afiliación
  • Liu Y; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China; School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
  • Ren J; Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab for Biomaterials, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Zhang W; Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China; Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Ding L; Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China; Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Ma R; Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Zhang M; Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Zheng S; Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Liang R; Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab for Biomaterials, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic addr
  • Zhang Y; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China; Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China. Electronic address: zhangyunlong02@westlake.edu.cn.
Biomaterials ; 312: 122707, 2025 Jan.
Article en En | MEDLINE | ID: mdl-39121729
ABSTRACT
Polypyrimidine tract-binding protein 1 (PTBP1) regulates numerous alternative splicing events during tumor progression and neurogenesis. Previously, PTBP1 downregulation was reported to convert astrocytes into functional neurons; however, how PTBP1 regulates astrocytic physiology remains unclear. In this study, we revealed that PTBP1 modulated glutamate uptake via ATP1a2, a member of Na+/K+-ATPases, and glutamate transporters in astrocytes. Ptbp1 knockdown altered mitochondrial function and energy metabolism, which involved PTBP1 regulating mitochondrial redox homeostasis via the succinate dehydrogenase (SDH)/Nrf2 pathway. The malfunction of glutamate transporters following Ptbp1 knockdown resulted in enhanced excitatory synaptic transmission in the cortex. Notably, we developed a biomimetic cationic triblock polypeptide system, i.e., polyethylene glycol44-polylysine30-polyleucine10 (PEG44-PLL30-PLLeu10) with astrocytic membrane coating to deliver Ptbp1 siRNA in vitro and in vivo, which approach allowed Ptbp1 siRNA to efficiently cross the blood-brain barrier and target astrocytes in the brain. Collectively, our findings suggest a framework whereby PTBP1 serves as a modulator in glutamate transport machinery, and indicate that biomimetic methodology is a promising route for in vivo siRNA delivery.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Astrocitos / Ácido Glutámico / Proteína de Unión al Tracto de Polipirimidina / Ribonucleoproteínas Nucleares Heterogéneas / ARN Interferente Pequeño / Factor 2 Relacionado con NF-E2 / Homeostasis Límite: Animals / Humans / Male Idioma: En Revista: Biomaterials Año: 2025 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Astrocitos / Ácido Glutámico / Proteína de Unión al Tracto de Polipirimidina / Ribonucleoproteínas Nucleares Heterogéneas / ARN Interferente Pequeño / Factor 2 Relacionado con NF-E2 / Homeostasis Límite: Animals / Humans / Male Idioma: En Revista: Biomaterials Año: 2025 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos