Protective effect of recombinant soluble neprilysin against ß-amyloid induced neurotoxicity.
Biochem Biophys Res Commun
; 477(4): 614-619, 2016 09 02.
Article
in En
| MEDLINE
| ID: mdl-27395340
ABSTRACT
A few decades ago, researchers found emerging evidence showing that a number of sequential events lead to the pathological cascade of Alzheimer's disease (AD) which is caused by the accumulation of amyloid beta (Aß), a physiological peptide, in the brain. Therefore, regulation of Aß represents a crucial treatment approach for AD. Neprilysin (NEP), a membrane metallo-endopeptidase, is a rate-limiting peptidase which is known to degrade the amyloid beta peptide. This study investigated soluble NEP (sNEP) produced by recombinant mammalian cells stably transfected with a non-viral NEP expression vector to demonstrate its protective effect against Aß peptides in neuronal cells in vitro. Stably transfected HEK 293 cells were used to purify the soluble protein. sNEP and Aß peptide co-treated hippocampal cells had a decreased level of Aß peptides shown by an increase in cell viability and decrease in apoptosis measured by the CCK-8 and relative caspase-3 activity ratio assays, respectively. This study shows that stably transfected mammalian cells can produce soluble NEP proteins which could be used to protect against Aß accumulation in AD and subsequently neuronal toxicity. Additionally, approaches using protein therapy for potential targets could change the pathological cascade of Alzheimer's disease.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neprilysin
/
Amyloid beta-Peptides
Limits:
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2016
Document type:
Article