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P1‐087: Cerebroprotective and Nootropic Effects of Brainact‐A2 in Animal Models Relevant to Alzheimer’s Disease
Author(s) -
Hanumanthacharjoshi Karichedu,
Mohammed Majed Alkanad
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.835
Subject(s) - ibotenic acid , morris water navigation task , hippocampus , neuroscience , pharmacology , nootropic , acetylcholinesterase , psychology , medicine , chemistry , central nervous system , biochemistry , enzyme
proteolytic cleavages operated on the amyloid precursor protein (APP). First, b-secretase (BACE1) cleaves APP at the N-terminal end of the Ab sequence to produce a secreted form of APP, named sAPPb, and a C-terminal membrane-bound 99-aminoacid fragment (C99). Then, g-secretase cleaves C99 within the transmembrane domain to release the Ab peptides of different lengths, predominantly Ab1-40 and Ab1-42.Methods:By using USA FDA approved drug library, we could discover putative therapeutic chemicals by cell based assay. TG reduced the levels of BACE1 protein and mRNA in APP-SH-SY5Y cells. In order to confirm the effect of TG regulate the expression BACE1, we were produced the RFP (BACE1 expression indicator) -GFP (cell body) U2OS cell line and compared the TG and analogs. Carried out Morris Water Maze(MWM) experiment by using APP/PS1 AD model mouse. we deal with immunofluorescence assay in both region of each group mouse brain. we conducted an ELISA assay to determine quantitative changes of Ab formation. Results: In the RFP-GFP-U20S cell line, the expression of RFP was reduced about 20% in 1mM TG treated group comparing to the control group. The expression of BACE1 was reduced gradually. This decreasing result was confirmed in both protein and mRNA expression. BACE1 expression was best reduced when TG was treated than any analog. WT and TG 0.5mg/kg group found the platform quickly and accurately compared to other groups. In addition, WTand TG 0.5mg/kg group stayed longer in target quadrant compared to the other groups. TG significantly reduced BACE1 expression in APP/PS1 mouse brain. The amount of the Ab42 and Ab40 was significantly reduced in group treated with TG. Conclusions: We found that TG reduces BACE1 expression in vitro as well as in vivo, which means that TG can mitigate Alzheimer’s disease neuropathy and be developed as a therapeutic agent for Alzheimer’s disease.