Articles
Vol. 70 No. 2 (2026)
Ketogenic diet regulates Uch-L1(C) to improve cerebral energy metabolism and cognitive function in Alzheimer's disease mice
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 20 April 2026
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The ketogenic diet (KD), a high-fat, low-carbohydrate diet, can effectively regulate energy metabolism in the brain. The regulation of cerebral energy metabolism in patients with Alzheimer's disease (AD) has attracted the attention of researchers. Recent studies have shown that ubiquitin carboxyl terminal hydrolase L1 (Uch-L1) deficiency leads to neurodegeneration by increasing energy demand and endoplasmic reticulum stress. However, the effect of Uch-L1 on AD remains to be explored. This study first combined Uch-L1 with cerebral energy metabolism to explore its role in long-term KD in AD. We found that AD mice with long-term KD showed better spatial recognition and working memory. KD promoted Uch-L1(C) and Mfn2 expression by inhibiting oxidative stress in the hippocampus of mice, improved mitochondrial function, increased ATP content, and significantly reduced neuronal apoptosis. In conclusion, KD can increase Uch-L1(C) and Mfn2 expression in the brain, and improve cerebral energy metabolism and cognitive function in AD mice.
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Ethics Approval
All animal experimental procedures were reviewed and approved by the Animal Ethics Committee of North Sichuan Medical CollegeCRediT authorship contribution
Nana Bao, Guohui Jiang, conceptualization, methodology, experiments design, proposed and secured funding for this project. Min Zhang, Ming Tang, Ziyi Shen, performed the research. Shenglin Wang, contributed to the analytic tools. Min Zhang, analyzed the data and wrote the article. Ming Tang, Shenglin Wang, Guohui Jiang, writing - review & editing. All authors contributed to the article and approved the final version.
Supporting Agencies
North Sichuan Medical College , Primary Health Development Research Center of Sichuan ProvinceData Availability Statement
The data supporting the conclusions of this article will be made available by contacting the corresponding author.
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1.
Bao N, Zhang M, Tang M, Shen Z, Wang S, Jiang G. Ketogenic diet regulates Uch-L1(C) to improve cerebral energy metabolism and cognitive function in Alzheimer’s disease mice. Eur J Histochem [Internet]. 2026 Apr. 20 [cited 2026 May 10];70(2). Available from: https://www.ejh.it/ejh/article/view/4548
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