A new therapeutic approach to treat Alzheimer's disease (AD) is needed, and the use of growth factors is considered to be a candidate. Hepatocyte growth factor (HGF) is a unique multifunctional growth factor, which has the potential effect to exert neurotrophic action and induce angiogenesis. In this study, we examined the effects of overexpression of human HGF plasmid DNA using ultrasound-mediated gene transfer into the brain in an Abeta-infused cognitive dysfunction mouse model. We demonstrated that HGF gene transfer significantly alleviated Abeta-induced cognitive impairment in mice in behavioral tests. These beneficial effects of HGF might be due to (1) significant recovery of the vessel density in the dentate gyrus of the hippocampus, (2) upregulation of BDNF, (3) a significant decrease in oxidative stress and (4) synaptic enhancement. A pharmacological approach including gene therapy to increase the HGF level in combination with anti-Abeta therapy might be a new therapeutic option for the treatment of AD.Gene Therapy (2008) 15, 561-571; doi:10.1038/sj.gt.3303094; published online 21 February 2008.
Alleviation of Abeta-induced cognitive impairment by ultrasound-mediated gene transfer of HGF in a mouse model. Publishing Authors By Initials
Alleviation of Abeta-induced cognitive impairment by ultrasound-mediated gene transfer of HGF in a mouse model. Journal Published:
PUBLICATION TYPE: Journal Article
Journal: Gene therapy
VOLUME: 15
Page Numbers: 561-71
Journal Abbreviation: Gene Ther.
ISSN: 1476-5462
DAY: 21
MONTH: 02
YEAR: 2008
Alleviation of Abeta-induced cognitive impairment by ultrasound-mediated gene transfer of HGF in a mouse model. Information
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LANGUAGE: eng
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AFFILIATION: [1] 1Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Japan [2] 2Department of Geriatric Medicine, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Japan.
Country: England
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