PURPOSE: The peptide-based delivery system constitutes a potent approach to overcome the limitations of drug delivery in vitro and in vivo. We recently proposed a novel peptide RDP, which enables brain-targeting delivery of proteins into neuronal cells. Here we investigate the possible internalization mechanism of RDP, and identify the therapeutic effects of functional proteins when linked with RDP in brain disease. METHODS: The RDP fusion proteins are produced through recombinant DNA technology, and cell culture is used to investigate the uptake mechanism of RDP and its fusion protein. Experimental Parkinson's disease (PD) model is prepared in mice by intra-striatal injection of 6-hydroxydopamine, and is tested by apomorphine- and amphetamine-induced rotation. RESULTS: The results suggest that the possible route for RDP cellular uptake might involve GABA receptor-dependent, clathrin-mediated endocytosis pathway. Additionally, the conjugate of RDP and glial cell-derived neurotrophic factor (GDNF) exhibits the neuroprotective effect in experimental PD animals, including reduction of apomorphine- and amphetamine-induced rotation following toxin administration. CONCLUSIONS: RDP may become an effective tool for the targeted delivery of proteins into brain for disease treatment.
PURPOSE: The peptide-based delivery system constitutes a potent approach to overcome the limitations of drug delivery in vitro and in vivo. We recently proposed a novel peptide RDP, which enables brain-targeting delivery of proteins into neuronal cells. Here we investigate the possible internalization mechanism of RDP, and identify the therapeutic effects of functional proteins when linked with RDP in brain disease. METHODS: The RDP fusion proteins are produced through recombinant DNA technology, and cell culture is used to investigate the uptake mechanism of RDP and its fusion protein. Experimental Parkinson's disease (PD) model is prepared in mice by intra-striatal injection of 6-hydroxydopamine, and is tested by apomorphine- and amphetamine-induced rotation. RESULTS: The results suggest that the possible route for RDP cellular uptake might involve GABA receptor-dependent, clathrin-mediated endocytosis pathway. Additionally, the conjugate of RDP and glial cell-derived neurotrophic factor (GDNF) exhibits the neuroprotective effect in experimental PD animals, including reduction of apomorphine- and amphetamine-induced rotation following toxin administration. CONCLUSIONS: RDP may become an effective tool for the targeted delivery of proteins into brain for disease treatment.
Authors: Shi-Rong Cai; Guang Xu; Michelle Becker-Hapak; Margaret Ma; Steven F Dowdy; Howard L McLeod Journal: Eur J Pharm Sci Date: 2006-01-11 Impact factor: 4.384
Authors: Gunnar P H Dietz; Paoloa C Valbuena; Birgit Dietz; Katrin Meuer; Patrick Müeller; Jachen H Weishaupt; Mathias Bähr Journal: Brain Res Date: 2006-04-12 Impact factor: 3.252
Authors: Paul A Gramlich; Wendy Westbroek; Ricardo A Feldman; Ola Awad; Nicholas Mello; Mary P Remington; Ying Sun; Wujuan Zhang; Ellen Sidransky; Michael J Betenbaugh; Paul S Fishman Journal: J Biotechnol Date: 2016-01-18 Impact factor: 3.307
Authors: Maria Francisca Coutinho; Juliana Inês Santos; Liliana S Mendonça; Liliana Matos; Maria João Prata; Amália S Jurado; Maria C Pedroso de Lima; Sandra Alves Journal: Int J Mol Sci Date: 2020-08-10 Impact factor: 5.923