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

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

  • Mol Nutr Food Res. 2023 May 16;e2200799. doi: 10.1002/mnfr.202200799.
Jianfeng Chen 1,  Yongsui Li 2,  Minyu Chen 1,  Xinwei Liu 1,  Jinghong Chen 1 3,  Xinlu Li 1,  Chao Wang 4,  Guohui Wan 5,  Jing Tian 1
Affiliations

Affiliations

  • 1 Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, 518055, China.
  • 2 Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.
  • 3 Shenzhen Bay Laboratory, Shenzhen, Guangdong, 518055, China.
  • 4 Chemical Analysis & Physical Testing Institute, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, 518055, China.
  • 5 National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, National Engineering Research Center for New Drug and Druggability (cultivation), Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, 510000, China.
PMID: 37194410 DOI: 10.1002/mnfr.202200799
Abstract

Scope: 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.

Methods and results: 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.

Conclusion: 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.

Keywords

Alzheimer's disease (AD); Cholesterol; Intestinal flora; Lipid raft; Pantethine.

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