Recombinant soluble neprilysin reduces amyloid-beta accumulation and improves memory impairment in Alzheimer's disease mice.

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.

Park MH ，Lee JK ，Choi S ，Ahn J ，Jin HK ，Park JS ，Bae JS ... -  《-》

Neprilysin deficiency alters the neuropathological and behavioral phenotype in the 5XFAD mouse model of Alzheimer's disease.

Hüttenrauch M ，Baches S ，Gerth J ，Bayer TA ，Weggen S ，Wirths O ... -  《-》

4-O-methylhonokiol attenuated memory impairment through modulation of oxidative damage of enzymes involving amyloid-β generation and accumulation in a mouse model of Alzheimer's disease.

Choi IS ，Lee YJ ，Choi DY ，Lee YK ，Lee YH ，Kim KH ，Kim YH ，Jeon YH ，Kim EH ，Han SB ，Jung JK ，Yun YP ，Oh KW ，Hwang DY ，Hong JT ... -  《-》

Self-assembling nanofibers alter the processing of amyloid precursor protein in a transgenic mouse model of Alzheimer's disease.

Yang H ，Yang H ，Xie Z ，Wang P ，Bi J ... -  《-》

A modified formulation of Chinese traditional medicine improves memory impairment and reduces Aβ level in the Tg-APPswe/PS1dE9 mouse model of Alzheimer's disease.

SuHeXiang Wan (SHXW), a Chinese traditional medicine has been used orally for the treatment of seizures, infantile convulsion, stroke and so forth. Previously, we reported the effects of modified SHXW essential oil mixture of the fragrance containing herbs on the sedative effect, anticonvulsant property and antioxidative activity after fragrance inhalation. This study was undertaken to evaluate beneficial effects of a modified recipe of SHXW (termed as KSOP1009) consisting of a ethanol extract of 8 herbs including resin of Liquidambar orientalis Miller, seed of Myristica fragrans Houtt., rhizome of Cnidium officinale Makino, lumber of Santalum album L., fructus of Piper longum L., flower buds of Eugenia caryophyllata Merrill et Perry, pollen of Typha orientalis Presl., and root of Salvia miltiorrhiza Bunge in the neurodegenerative diseases such as Alzheimer's disease (AD). The transgenic mice of AD, Tg-APPswe/PS1dE9, were fed KSOP1009 or as a positive control, donepezil for 3 months from 4.5 months of age. Behavioral, immunological and ELISA analyses were used to assess memory impairment, Aβ accumulation and plaque deposition in the brain. Other in vitro works were performed to examine whether KSOP1009 inhibits the Aβ(1-42)-induced neurotoxicity in human neuroblastoma cell line, SH-SY5Y cells. Intake of KSOP1009 improved the Aβ-induced memory impairment and suppressed Aβ levels and plaque deposition in the brain of Tg-APPswe/PS1dE9 mice as much as that of donepezil treatment. KSOP1009 prevented the down-regulation of phospho-CREB and increased AKT phosphorylation in the AD-like brains. Moreover, KSOP1009 suppresses Aβ-induced apoptosis and ROS production in SH-SY5Y cells. The present study suggests that KSOP1009 may develop as a therapeutic drug for treatment of AD patients.

Jeon S ，Bose S ，Hur J ，Jun K ，Kim YK ，Cho KS ，Koo BS ... -  《-》