title: Cellular uptake mechanism and therapeutic utility of a novel peptide in targeted-delivery of proteins into neuronal cells.
abstract: OBJECTIVE
  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.affiliation: School of Pharmaceutical Sciences, Southwest University, Tian Sheng Road, Beibei District, Chongqing 400716, China. Fuailing1008@yahoo.com.cn
authors.forename: Ailing
authors.initials: A
authors.lastname: Fu
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Zhao
authors.forename: Feiyan
authors.initials: F
authors.lastname: Gao
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D016503:Drug Delivery Systems; D004705:Endocytosis; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D010455:Peptides; D011993:Recombinant Fusion Proteins; D005680:gamma-Aminobutyric Acid