DJ1 Ameliorates AD-like Pathology in the Hippocampus of APP/PS1 Mice.

Yang Yang PENG; Meng Xin LI; Wen Jie LI; Yuan XUE; Yu Fan MIAO; Yu Lin WANG; Xiao Chen FAN; Lu Lu TANG; Han Lu SONG; Qian ZHANG; Xing LI

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DJ1 Ameliorates AD-like Pathology in the Hippocampus of APP/PS1 Mice.

Author: Yang Yang PENG ¹ ; Meng Xin LI ¹ ; Wen Jie LI ¹ ; Yuan XUE ¹ ; Yu Fan MIAO ¹ ; Yu Lin WANG ¹ ; Xiao Chen FAN ¹ ; Lu Lu TANG ¹ ; Han Lu SONG ¹ ; Qian ZHANG ² ; Xing LI ¹
Author Information

1. Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.
2. The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Publication Type:Journal Article
Keywords: AMPK/mTOR; Alzheimer’s disease; Apoptosis.; Autophagy; DJ1; NRF2/HO-1; Oxidative stress
MeSH: Animals; Mice; Alzheimer Disease/therapy*; AMP-Activated Protein Kinases/metabolism*; Amyloid beta-Protein Precursor/metabolism*; Antioxidants/metabolism*; Disease Models, Animal; Hippocampus/metabolism*; Kelch-Like ECH-Associated Protein 1/metabolism*; Mammals/metabolism*; Mice, Inbred C57BL; Mice, Transgenic; NF-E2-Related Factor 2/metabolism*; Presenilin-1/metabolism*; TOR Serine-Threonine Kinases/metabolism*
From: Biomedical and Environmental Sciences 2023;36(11):1028-1044
CountryChina
Language:English
Abstract: OBJECTIVE:To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD.
METHODS:Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 ⁺), and DJ1-knockdown group (DJ1 ^-). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice.
RESULTS:DJ1 ⁺ overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 ^- cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 ⁺ increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA).
CONCLUSION:DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.