title: BACE1 RNA interference improves spatial memory and attenuates Aβ burden in a streptozotocin-induced tau hyperphosphorylated rat model.
abstract: Both senile plaques and intracellular neurofibrillary tangles are important pathological characteristics in Alzheimer's disease. However, the relationship between Aβ deposition and tau hyperphosphorylation is unknown. In this study, the increased levels of full-length amyloid precursor protein (APP), APP C-terminal fragment (β-CTF) and BACE1 were found in streptozotocin-induced tau hyperphosphorylation models by quantitative polymerase chain reaction, Western blotting and immunohistochemistry methods. In the previous studies, few strategies focusing on inhibiting β-secretase (BACE1) in a tau hyperphosphorylation model were utilized. Here, BACE1 RNAi was used to treat the streptozotocin-induced tau hyperphosphorylation animal models. BACE1 RNAi treatment improved the behavioural ability of animal models and reduced the amount of Aβ1-40 and Aβ1-42, accompanied by decreasing the levels of BACE1 and β-CTF. Our results demonstrated that neurological defects and neurotoxic fragments, including Aβ and β-CTF, were eliminated by BACE1 RNAi in the tau hyperphosphorylated model, implying the efficiency and safety of BACE1RNAi treatment against Alzheimer's disease.
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Chun-Jiang
authors.initials: CJ
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Zhi-Ren
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory; D013311:Streptozocin; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D013311:Streptozocin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat
keywords: Alzheimer's disease; BACE1; RNA interference; amyloid beta; tau