N. Bao, M. Zhang, M. Tang, Z. Shen, S. Wang and G. Jiang (2026). Ketogenic diet regulates Uch-L1(C) to improve cerebral energy metabolism and cognitive function in Alzheimer's disease mice. European journal of histochemistry : EJH, 70(2). https://doi.org/10.4081/ejh.2026.4548

PubMed 42007524

[Abstract]
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.