Thioredoxin 1 plays a beneficial role in Alzheimer's disease by regulating endoplasmic reticulum stress

Abstract

Abstract Alzheimer's disease (AD), a neurodegenerative disease, has a complex pathological mechanism involving oxidative stress, endoplasmic reticulum (ER) stress and other pathways. Thioredoxin 1 (Trx-1), the major redox regulator, may be an effective treatment strategy for AD. Therefore, the present study explored the role and possible mechanism of Trx-1 in AD. The expression of Trx-1 in the hippocampus of AD was verified by WB and RT-PCR, and the effects of Trx-1 on behavioral function and neuropathological damage of AD mice were analyzed by open field test, water maze experiment, HE staining, and protein expression analysis of amyloid β-protein (Aβ), Tau protein (Tau) and p-Tau. At the same time, oxygen species (ROS) and ER stress were detected to further analyze the mechanism. Trx-1 expression in the hippocampus of AD model mice was reduced, and the oe-Trx-1 remarkably enhanced it. We observed an obvious behavioral cognitive dysfunction and neuropathological damage in AD model mice. Trx-1 significantly ameliorated the anxiety-like behavior and cognitive ability in AD mice, alleviated the pathological damage of hippocampal tissue, and reduced the protein expressions of Aβ, Tau, and p-Tau, suggesting that Trx-1 could alleviate behavioral cognitive dysfunction and neuropathological damage in AD. In addition, Trx-1 significantly reduced ROS levels and the GRP78, PERK, IRE1α, and CHOP protein expression and relieved ER stress in AD mice. Trx-1 may alleviate behavioral cognitive dysfunction and neuropathological damage in AD mice by regulating ER stress.