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Systemic Treatment with Fas-Blocking Peptide Attenuates Apoptosis in Brain Ischemia.
Chung, Sungeun; Yi, Yujong; Ullah, Irfan; Chung, Kunho; Park, Seongjun; Lim, Jaeyeoung; Kim, Chaeyeon; Pyun, Seon-Hong; Kim, Minkyung; Kim, Dokyoung; Lee, Minhyung; Rhim, Taiyoun; Lee, Sang-Kyung.
Afiliación
  • Chung S; Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea.
  • Yi Y; Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea.
  • Ullah I; Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea.
  • Chung K; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
  • Park S; Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea.
  • Lim J; Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
  • Kim C; Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea.
  • Pyun SH; Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea.
  • Kim M; Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea.
  • Kim D; Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea.
  • Lee M; Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea.
  • Rhim T; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
  • Lee SK; Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea.
Int J Mol Sci ; 25(1)2024 Jan 04.
Article en En | MEDLINE | ID: mdl-38203830
ABSTRACT
Apoptosis plays a crucial role in neuronal injury, with substantial evidence implicating Fas-mediated cell death as a key factor in ischemic strokes. To address this, inhibition of Fas-signaling has emerged as a promising strategy in preventing neuronal cell death and alleviating brain ischemia. However, the challenge of overcoming the blood-brain barrier (BBB) hampers the effective delivery of therapeutic drugs to the central nervous system (CNS). In this study, we employed a 30 amino acid-long leptin peptide to facilitate BBB penetration. By conjugating the leptin peptide with a Fas-blocking peptide (FBP) using polyethylene glycol (PEG), we achieved specific accumulation in the Fas-expressing infarction region of the brain following systemic administration. Notably, administration in leptin receptor-deficient db/db mice demonstrated that leptin facilitated the delivery of FBP peptide. We found that the systemic administration of leptin-PEG-FBP effectively inhibited Fas-mediated apoptosis in the ischemic region, resulting in a significant reduction of neuronal cell death, decreased infarct volumes, and accelerated recovery. Importantly, neither leptin nor PEG-FBP influenced apoptotic signaling in brain ischemia. Here, we demonstrate that the systemic delivery of leptin-PEG-FBP presents a promising and viable strategy for treating cerebral ischemic stroke. Our approach not only highlights the therapeutic potential but also emphasizes the importance of overcoming BBB challenges to advance treatments for neurological disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Isquemia Encefálica / Accidente Cerebrovascular Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article Pais de publicación: Suiza
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: Isquemia Encefálica / Accidente Cerebrovascular Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article Pais de publicación: Suiza