Pantethine ameliorates recognition impairment in a mouse model of Alzheimer's disease by modulating cholesterol content and intestinal flora species.

Abstract

As a natural dietary low-molecular-weight thiol, pantethine helps maintain brain homeostasis and function in AD mice. The current study aimed to investigate the protective effects and underlying mechanisms of pantethine on the mitigation of cognitive deficits and pathology in a triple transgenic AD mouse model. Compared to control mice, oral administration of pantethine improved spatial learning and memory ability, relieved anxiety, and reduced the production of Aβ, neuronal damage, and inflammation in 3×Tg-AD mice. Pantethine reduced body weight, body fat, and the production of cholesterol in 3×Tg-AD mice by inhibiting SREBP2 signal pathway and APOE expression; lipid rafts in the brain, which are necessary for the processing of the Aβ precursor APP, were also decreased. In addition, pantethine regulated the composition, distribution, and abundance of characteristic flora in the intestine; these flora are considered protective and anti-inflammatory in the gastrointestinal tract, suggesting a possible improvement in the gut flora of 3×Tg-AD mice. This study highlights the potential therapeutic effect of pantethine in AD by reducing cholesterol and lipid raft formation and regulating intestinal flora, suggesting a new option for the development of clinical drugs for AD. This article is protected by copyright. All rights reserved.