ArticleJournal of Alzheimer's disease : JAD2021
Partial Inhibition of Mitochondrial Complex I Reduces Tau Pathology and Improves Energy Homeostasis and Synaptic Function in 3xTg-AD Mice.
Article in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Mitochondrial quality control in health and disease: Updates 2026.Chinese medical journal · 2026Review
- Discovery and preclinical validation of a translationally optimized mitochondrial complex I modulator for Alzheimer's disease.npj drug discovery · 2026Article
- Mitochondrial Dysfunction in Alzheimer's Disease and Mitochondria-Targeted Therapeutics.Cells · 2026Review
- Discovery and Preclinical Validation of a Clinically Optimized Mitochondrial Complex I Modulator for Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Hub genes and diagnostic model associated with mitochondrial function in Alzheimer's disease.Animal models and experimental medicine · 2026Article
- Mitochondrial complex I deficiency induces Alzheimer's disease-like signatures that are reversible by targeted therapy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Neuroprotective mitochondria targeted small molecule restores synapses and the distribution of synaptic mitochondria in the hippocampus of APP/PS1 mice.Scientific reports · 2025Article
- Non-invasive MRI of blood-cerebrospinal fluid-barrier function in a mouse model of Alzheimer's disease: a potential biomarker of early pathology.Fluids and barriers of the CNS · 2024Article
- The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing.Translational neurodegeneration · 2024Review
- Mitochondria-Related Candidate Genes and Diagnostic Model to Predict Late-Onset Alzheimer's Disease and Mild Cognitive Impairment.Journal of Alzheimer's disease : JAD · 2024Article
- Mitochondrial Complex I and β-Amyloid Peptide Interplay in Alzheimer's Disease: A Critical Review of New and Old Little Regarded Findings.International journal of molecular sciences · 2023Review
- Administration of recombinant FOXN1 protein attenuates Alzheimer's pathology in mice.Brain, behavior, and immunity · 2023Article
- Axonal energy metabolism, and the effects in aging and neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- Systemic Metabolism and Mitochondria in the Mechanism of Alzheimer's Disease: Finding Potential Therapeutic Targets.International journal of molecular sciences · 2023Review
- Article
- Modulation of Mitochondrial Function as a Therapeutic Strategy for Neurodegenerative Diseases.The journal of prevention of Alzheimer's disease · 2023Review
- The use of fibroblasts as a valuable strategy for studying mitochondrial impairment in neurological disorders.Translational neurodegeneration · 2022Review
- Advances in Recapitulating Alzheimer's Disease Phenotypes Using Human Induced Pluripotent Stem Cell-Based In Vitro Models.Brain sciences · 2022Review
- Mitochondrial complex I as a therapeutic target for Alzheimer's disease.Acta pharmaceutica Sinica. B · 2022Review
- Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease.Acta pharmaceutica Sinica. B · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAccumulation of hyperphosphorylated tau (pTau) protein is associated with synaptic dysfunction in Alzheimer's disease (AD). We previously demonstrated that neuroprotection in familial mouse models of AD could be achieved by targeting mitochondria complex I (MCI) and activating the adaptive stress response. Efficacy of this strategy on pTau-related pathology remained unknown.
objectiveTo investigate the effect of specific MCI inhibitor tricyclic pyrone compound CP2 on levels of human pTau, memory function, long term potentiation (LTP), and energy homeostasis in 18-month-old 3xTg-AD mice and explore the potential mechanisms.
methodsCP2 was administered to male and female 3xTg-AD mice from 3.5-18 months of age. Cognitive function was assessed using the Morris water maze. Glucose metabolism was measured in periphery using a glucose tolerance test and in the brain using fluorodeoxyglucose F18 positron-emission tomography (FDG-PET). LTP was evaluated using electrophysiology in the hippocampus. The expression of key proteins associated with neuroprotective mechanisms were assessed by western blotting.
resultsChronic CP2 treatment restored synaptic activity in female 3xTg-AD mice; cognitive function, levels of synaptic proteins, glucose metabolism, and energy homeostasis were improved in male and female 3xTg-AD mice. Significant reduction of human pTau in the brain was associated with increased activity of protein phosphatase of type 2A (PP2A), and reduced activity of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3β (GSK3β).
conclusionCP2 treatment protected against synaptic dysfunction and memory impairment in symptomatic 3xTg-AD mice, and reduced levels of human pTau, indicating that targeting mitochondria with small molecule specific MCI inhibitors represents a promising strategy for treating AD.
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Registered trials
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