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Functional modification of recombinant brain-derived neurotrophic factor and its protective effect against neurotoxicity.
Liu, Chang; Yan, Qi; Ding, Xuying; Zhao, Meijun; Chen, Chen; Zheng, Qian; Yang, Huiying; Xie, Yining.
Afiliação
  • Liu C; College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China. Electronic address: liuchangbhu@163.com.
  • Yan Q; College of Pharmaceutical Science, Jilin University, Changchun 130021, China.
  • Ding X; College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China.
  • Zhao M; Department of Clinical Pharmacy, Affiliated Hospital of Jilin Medical College, Jilin, Jilin 132013, PR China.
  • Chen C; Affiliated Hospital of Yanbian university, Yanji, Jilin 133002, PR China.
  • Zheng Q; College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China.
  • Yang H; College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China.
  • Xie Y; College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China.
Int J Biol Macromol ; 267(Pt 2): 131610, 2024 May.
Article em En | MEDLINE | ID: mdl-38621565
ABSTRACT
Brain-derived neurotrophic factor (BDNF) is a neurotrophic protein that promotes neuronal survival, increases neurotransmitter synthesis, and has potential therapeutic effects in neurodegenerative and psychiatric diseases, but its drug development has been limited by the fact that recombinant proteins of BDNF are unstable and do not penetrate the blood-brain barrier (BBB). In this study, we fused a TAT membrane-penetrating peptide with BDNF to express a recombinant protein (TBDNF), which was then PEG-modified to P-TBDNF. Protein characterization showed that P-TBDNF significantly improved the stability of the recombinant protein and possessed the ability to penetrate the BBB, and in cellular experiments, P-TBDNF prevented MPTP-induced nerve cell oxidative stress damage, apoptosis and inflammatory response, and its mechanism of action was closely related to the activation of tyrosine kinase B (TrkB) receptor and inhibition of microglia activation. In animal experiments, P-TBDNF improved motor and cognitive deficits in MPTP mice and inhibited pathological changes in Parkinson's disease (PD). In conclusion, this paper is expected to reveal the mechanism of action of P-TBDNF in inhibiting neurotoxicity, provide a new way for treating PD, and lay the foundation for the future development of recombinant P-TBDNF.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fármacos Neuroprotetores / Fator Neurotrófico Derivado do Encéfalo Limite: Animals / Humans / Male Idioma: En Revista: Int J Biol Macromol Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fármacos Neuroprotetores / Fator Neurotrófico Derivado do Encéfalo Limite: Animals / Humans / Male Idioma: En Revista: Int J Biol Macromol Ano de publicação: 2024 Tipo de documento: Article