title: Recombinant DNA vaccine against neurite outgrowth inhibitors attenuates behavioral deficits and decreases Abeta in an Alzheimer's disease mouse model.
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 Aβ 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.
authors.affiliation: Comparative Medicine Center, Peking Union Medical College and Institute of Laboratory Animal Science, Chinese Academy of Medical Science, No 5 Pan Jia Yuan Nan Li, Chaoyang District, Beijing 100021, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Ma
authors.forename: Wulin
authors.initials: W
authors.lastname: Yang
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Qi
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Yao
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Chunmei
authors.initials: C
authors.lastname: Ma
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Yingying
authors.initials: Y
authors.lastname: Gao
authors.forename: Li
authors.initials: L
authors.lastname: Ruan
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000523:psychology* / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes; D001526:Behavioral Symptoms / Q000517:prevention & control*; D018728:Entorhinal Cortex / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D005911:Gliosis / Q000473:pathology / Q000517:prevention & control; D006624:Hippocampus / Q000473:pathology / Q000648:ultrastructure; D007106:Immune Sera / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors*; D058225:Plaque, Amyloid / Q000517:prevention & control; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D016229:Amyloid beta-Peptides; D007106:Immune Sera; D009414:Nerve Growth Factors; D019444:Vaccines, DNA