title: Amelioration of dementia induced by Aβ 22-35 through rectal delivery of undecapeptide-hEGF to mouse brain.
abstract: A group of growth factors have been shown to play important roles in amelioration of the malfunction of the neurodegenerative diseases. However, the proteins or polypeptides passing across the blood-brain barrier (BBB) to access the brain parenchyma are relatively few so that it hinders the therapies in clinic. Here a genetically reconstructed fusion peptide of human epidermal growth factor (hEGF) with an undecapeptide YGRKKRRQRRR (P11) was used to investigate the permeability between the cell membrane and the BBB via rectal administration. The efficiency to rescue the Aβ 22-35-induced dementia in mice was assessed after administration of P11-hEGF per rectal. Our results showed that P11-hEGF permeates across not only the 3T3 cell membrane in vitro, but also the endothelia of vessels after intravenous injection (IV), and the mucosa of the rectum after per rectal administration. Further results showed that the circulating P11-hEGF allowed penetrating through the blood-brain barrier and then getting into the brain manifesting biological responses. In the animal experiments, treatment with P11-hEGF not only ameliorated the dementia induced by Aβ 22-35 but also rescued the dementia of the aged mice, no matter how it was administrated (IV or per rectal). These results suggest that the rectal non-invasive delivery of the P11 polypeptide-conjugated growth factor is an efficient way for BBB transduction, thus raises the hope of real therapeutic progress against neurodegenerative diseases.
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military, Medical Sciences, Beijing 100850, China.
authors.forename: Bao-Quan
authors.initials: BQ
authors.lastname: Zhao
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Guo
authors.forename: Xu-Ling
authors.initials: XL
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Zang
authors.forename: Heng-Yan
authors.initials: HY
authors.lastname: Qu
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhou
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Man-Ji
authors.initials: MJ
authors.lastname: Sun
mesh_terms: D000285:Administration, Rectal; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003704:Dementia / Q000188:drug therapy* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007859:Learning Disabilities / Q000188:drug therapy; D008569:Memory Disorders / Q000188:drug therapy; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D009842:Oligopeptides; C560082:P11-hEGF fusion protein; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor