Poster: Regulation of gene expression
Abs #
765: Expression analysis of plant-derived multimeric form of human Ab42: a step towards edible vaccine against Alzheimer disease
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Presenter: |
Jungwon, Youm |
Authors | Jungwon, Youm (A) Jaeheung, Jeon (A) Misun, Kim (A) Youngho, Kim (B) Inhee, Mook-Joung (B) Hyouk, Joung (A) Hyunsoon, Kim (A) | | Affiliations: |
(A): Lab. of Plant Cell Biotechnology, Korea Research Institute of Bioscience and Biotechnology
(B): Brain Disease Research Center, Digital Biotech (co.)
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Alzheimer¡¯s disease (AD) is characterized by the build-up of plaques comprised of insoluble b-amyloid peptide in the brain. The accumulated amyloid appears to damage neurons, which leads to the degeneration of synapses degenerate and, eventually, the neurons die. Therefore, reducing the accumulation of b-amyloid may prevent or delay the onset of AD. Recently, a novel immunotherapeutic approaches has been investigated to prevent AD by Schenk et al. and Morgan et al.. They immunized transgenic mice using purified b-amyloid itself and this new approach has been shown to raise an antibody against the 42 amino acid form of b-amyloid in different transgenic animal models of AD. Finally, the use of this antibody reduced plaque formation in the brain. In the previous studies, we developed plants expressing Ab42 form, but no specific reaction on western blotting was detected in any of the plant extracts analyzed, probably due to the small size of b-amyloid produced and the low levels of recombinant b-amyloid protein expression. At this time, we tried to modify the monomer of Ab42 itself to tandem repeatedly multimer (multimeric form) and introduced into three different kinds of expression vectors. We transformed potato and tomato with A. tumefaciens to generate transgenic plants for an antigen of b-amyloid. Copy numbers of the multimer Ab transgene were verified by Southern blot and specific transcript was confirmed by northern blot. The multimeric protein (about 20 KDa) was detected by western blot and ELISA. We orally immunized BALB/c mice by feeding transgenic plants expressing mutimeric form of Ab42 or non-transgenic plants with cholera toxin adjuvant. Our study forms a basis for exploring the ability of Ab42 to develop plant-derived edible vaccines against AD.
