Transduced PTD-BDNF fusion protein protects against beta amyloid peptide-induced learning and memory deficits in mice.
Brain-derived neurotrophic factor (BDNF) promotes the survival and differentiation of hippocampal, cortical, and basal forebrain cholinergic neurons. However, the efficacy of BDNF via peripheral (i.v.) administration is limited by the lack of transport of the neurotrophin through the blood-brain barrier (BBB) in vivo. The present study describes that the i.v. administered recombinant human BDNF (rhBDNF) conjugated with a protein transduction domain (PTD ) is able to survive and promote the growth of hippocampal neurons impaired by Abeta25-35 (10 microM) in vitro and transport through the BBB in vivo. The Morris water maze test indicated that the i.v. PTD-rhBDNF improved the spatial learning and memory of mice impaired by the aggregated Abeta25-35. The peripherally administered PTD-rhBDNF exhibited neuroprotective effects in brain and raise the possibility of delivery of the exogenous rhBDNF in treatment of the brain diseases.
Zhou
Jian Ping
JP
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
Feng
Ze Guo
ZG
Yuan
Ben Li
BL
Yu
Shou Zhong
SZ
Li
Qian
Q
Qu
Hen Yan
HY
Sun
Man Ji
MJ
D016229:Amyloid beta-Peptides; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism*; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D007859:Learning Disabilities / Q000139:chemically induced / Q000517:prevention & control*; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism; D010446:Peptide Fragments; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins; D014161:Transduction, Genetic / Q000379:methods
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C074636:amyloid beta-protein (25-35)