Recombinant DNA vaccine against neurite outgrowth inhibitors attenuates behavioral deficits and decreases Abeta in an Alzheimer's disease mouse model

LingLing Zhang, Quanhong Ma, Wulin Yang, Xiangrong Qi, Zhigang Yao, Ying Liu, Liang Liang, Xiang Wang, Chunmei Ma, Lan Huang, Yanfeng Xu, Hua Zhu, Wei Deng, Yingying Gao, Li Ruan, Zhicheng Xiao, Chuan Qin

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

Alzheimer s disease (AD) is a chronic neurodegenerative disease that causes a progressive loss in learning and memory capabilities and eventually results in dementia. The non-renewable nature of neurons in the central nervous system leads to the basic pathological changes that are related to the various behavioral and psychological symptoms of AD. Oligodendrocyte- and myelin-related neurite outgrowth inhibitors (NOIs) tend to hinder the regeneration of neurons. We designed a recombinant DNA vaccine composed of multiple specific inhibitory domains of NOIs. Vaccination induced effective antibodies against the specific domains in the sera of mice treated with a DNA primed-vaccinia virus boost regimen. The vaccine attenuated neuronal degeneration in the mouse brain and protected the model mice from behavioral deficits. Vaccination also decreased the formation of soluble Abeta oligomer and amyloid plaques in the co-transgenic mice brain. What s more, astrocytosis in brains of APP/PS1 co-transgenic mice was also relieved. The results suggested that immunotherapy with multiple specific domains of myelin- and oligodendrocyte-related NOIs may be a promising approach for Alzheimer s disease and other degenerative central nervous system diseases.
Original languageEnglish
Pages (from-to)200 - 210
Number of pages11
JournalNeuropharmacology
Volume70
DOIs
Publication statusPublished - 2013

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