Recombinant soluble neprilysin reduces amyloid-beta accumulation and improves memory impairment in Alzheimer's disease mice.
Brain Res
; 1529: 113-24, 2013 Sep 05.
Article
in En
| MEDLINE
| ID: mdl-23831521
ABSTRACT
Accumulation of amyloid-ß (Aß) 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 Aß-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 Aß in AD. Previous studies have utilized viral vectors expressing NEP for reduction of Aß 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 Aß. 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 Aß deposition and suggest the possibility that approaches using protein therapy might have potential for development of alternative therapies for treatment of AD.
Key words
Full text:
1
Collection:
01-internacional
Health context:
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Peptide Fragments
/
Antipsychotic Agents
/
Neprilysin
/
Amyloid beta-Peptides
/
Memory Disorders
Type of study:
Etiology_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Brain Res
Year:
2013
Document type:
Article