Back to Search
Start Over
miR-204-3p/Nox4 Mediates Memory Deficits in a Mouse Model of Alzheimer’s Disease
- Source :
- Mol Ther
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Alzheimer’s disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly, and the mechanisms of AD are not fully defined. MicroRNAs (miRNAs) have been shown to contribute to memory deficits in AD. In this study, we identified that miR-204-3p was downregulated in the hippocampus and plasma of 6-month-old APPswe/PS1dE9 (APP/PS1) mice. miR-204-3p overexpression attenuated memory and synaptic deficits in APP/PS1 mice. The amyloid levels and oxidative stress were decreased in the hippocampus of APP/PS1 mice after miR-204-3p overexpression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4) was a target of miR-204-3p, and Nox4 inhibition by GLX351322 protected neuronal cells against Aβ(1–42)-induced neurotoxicity. Furthermore, GLX351322 treatment rescued synaptic and memory deficits, and decreased oxidative stress and amyloid levels in the hippocampus of APP/PS1 mice. These results revealed that miR-204-3p attenuated memory deficits and oxidative stress in APP/PS1 mice by targeting Nox4, and miR-204-3p overexpression and/or Nox4 inhibition might be a potential therapeutic strategy for AD treatment.
- Subjects :
- medicine.medical_specialty
Amyloid
Hippocampus
Mice, Transgenic
medicine.disease_cause
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Alzheimer Disease
Internal medicine
mental disorders
Drug Discovery
Genetics
medicine
Animals
Dementia
Molecular Biology
030304 developmental biology
Pharmacology
Memory Disorders
0303 health sciences
Oxidase test
Amyloid beta-Peptides
business.industry
Neurotoxicity
NOX4
medicine.disease
Disease Models, Animal
MicroRNAs
Oxidative Stress
Endocrinology
nervous system
chemistry
NADPH Oxidase 4
030220 oncology & carcinogenesis
Molecular Medicine
Original Article
Disease Susceptibility
business
Biomarkers
Oxidative stress
Nicotinamide adenine dinucleotide phosphate
Subjects
Details
- ISSN :
- 15250016
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy
- Accession number :
- edsair.doi.dedup.....f32b5c2a261409a95397ddfc8225ea81