title: Recombinant soluble neprilysin reduces amyloid-beta accumulation and improves memory impairment in Alzheimer's disease mice.
abstract: Accumulation of amyloid-β (Aβ) is thought to be a central pathology in the brain of patients with Alzheimer's disease (AD). Neprilysin (NEP), a plasma membrane glycoprotein of the neutral zinc metalloendopeptidase family, is known as a major Aβ-degrading enzyme in the brain. The level of NEP is reduced in the brains of patients with AD; therefore, NEP is under intense investigation as a potential therapeutic source for degradation of deposited Aβ in AD. Previous studies have utilized viral vectors expressing NEP for reduction of Aβ deposition in the brain. However, viral vectors have disadvantages regarding difficulty in control of insert size, expression desired (short- or long-term), and target cell type. Here, in order to overcome these disadvantages, we produced recombinant soluble NEP from insect cells using an NEP expression vector, which was administered by intracerebral injection into AD mice, resulting in significantly reduced accumulation of Aβ. In addition, AD mice treated with NEP showed improved behavioral performance on the water maze test. These data support a role of recombinant soluble NEP in improving memory impairment by regulation of Aβ deposition and suggest the possibility that approaches using protein therapy might have potential for development of alternative therapies for treatment of AD.
authors.affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, South Korea.
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Jong Kil
authors.initials: JK
authors.lastname: Lee
authors.forename: Sunghyun
authors.initials: S
authors.lastname: Choi
authors.forename: Junseong
authors.initials: J
authors.lastname: Ahn
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Jin
authors.forename: Jong-Sang
authors.initials: JS
authors.lastname: Park
authors.forename: Jae-sung
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D020287:In Situ Nick-End Labeling; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D015260:Neprilysin / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D014150:Antipsychotic Agents; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D011994:Recombinant Proteins; C075222:amyloid beta-protein (1-42); D015260:Neprilysin
keywords: Alzheimer's disease model; Amyloid-β; Protein delivery; Recombinant soluble neprilysin