DJ1 Ameliorates AD-like Pathology in the Hippocampus of APP/PS1 Mice / 生物医学与环境科学(英文)
Biomedical and Environmental Sciences
; (12): 1028-1044, 2023.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-1007879
Responsible library:
WPRO
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.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Mice, Transgenic
/
Amyloid beta-Protein Precursor
/
Disease Models, Animal
/
NF-E2-Related Factor 2
/
Presenilin-1
/
AMP-Activated Protein Kinases
/
TOR Serine-Threonine Kinases
/
Alzheimer Disease
/
Kelch-Like ECH-Associated Protein 1
/
Hippocampus
Limits:
Animals
Language:
English
Journal:
Biomedical and Environmental Sciences
Year:
2023
Document type:
Article