ArticleCommunications biology2021
Partial inhibition of mitochondrial complex I ameliorates Alzheimer's disease pathology and cognition in APP/PS1 female mice.
Erratum issuedOpen access · goldAbstract read
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Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers.
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52citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
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Who cites it
52 citing papers in PubMed, 65 citations in OpenAlex.
- Revisiting Alzheimer's Disease Through the Somatostatin-Mitochondria Axis.Molecular neurobiology · 2026Review
- Discovery and preclinical validation of a translationally optimized mitochondrial complex I modulator for Alzheimer's disease.npj drug discovery · 2026Article
- Short-lived Niemann-Pick type C mice with accelerated brain aging as a novel model for Alzheimer's disease research.Neural regeneration research · 2026Article
- Discovery and Preclinical Validation of a Clinically Optimized Mitochondrial Complex I Modulator for Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Allele-specific splicing modulates protein isoforms and Alzheimer's risk.bioRxiv : the preprint server for biology · 2026Article
- Synaptic mitochondrial dysfunction and Alzheimer's disease: from molecular mechanisms to therapeutic strategies.Frontiers in pharmacology · 2026Review
- Onion-Mitochondria Inhibit Lipopolysaccharide-Induced Acute Lung Injury by Shaping Lung Macrophage Mitochondrial Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tau pathology in the brainstem monoaminergic neurons reflect resilience to Alzheimer's disease pathology in the Nun study cases.Acta neuropathologica communications · 2025Article
- Region-specific proteomic analysis of aging rhesus macaques following chronic glutamate-carboxypeptidase-II (GCPII) inhibition elucidates potential treatment strategies for sporadic Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Postnatal developmental dynamics of mitochondrial complex I in mouse tissues.American journal of physiology. Cell physiology · 2025Article
- Unveiling Moxibustion's Impact on AD Mice Learning and Memory: Role of Mitochondrial Respiratory Chain Complex I Subunit in the Hippocampus.Molecular neurobiology · 2025Article
- A consensus guide to preclinical indirect calorimetry experiments.Nature metabolism · 2025Review
- 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
- Article
- Pyrrolidine Dithiocarbamate Ameliorates Sepsis-Associated Encephalopathy by Inhibiting Autophagy and Inflammation in the Brain.Neurochemical research · 2025Article
- Neuroprotective mitochondria targeted small molecule restores synapses and the distribution of synaptic mitochondria in the hippocampus of APP/PS1 mice.Scientific reports · 2025Article
- Isolation of Intact Mitochondria FromBio-protocol · 2025Article
- Hormonal modulation, mitochondria and Alzheimer's prevention: the role of GLP-1 agonists and estrogens.Frontiers in molecular biosciences · 2025Review
- Chronological Dynamics of Neuroinflammatory Responses in a High-Fat Diet Mouse Model.International journal of molecular sciences · 2024Article
- Low to moderate ethanol exposure reduces astrocyte-induced neuroinflammatory signaling and cognitive decline in presymptomatic APP/PS1 mice.Scientific reports · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
36 authors at 6 institutions in 2 countries.
Andrea Stojakovic *Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Sergey Trushin *Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Anthony Sheu *Institute for Translational Neuroscience, University of Minnesota Twin Cities, 2101 6th Street SE, Minneapolis, MN, 55455, USA.
Layla KhaliliDepartment of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Su-Youne ChangDepartment of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Xing LiDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.ORCID http://orcid.org/0000-0002-8541-8363
Trace ChristensenMicroscopy and Cell Analysis Core, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Jeffrey L SalisburyMicroscopy and Cell Analysis Core, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Rachel E GerouxDepartment of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Benjamin GatenoDepartment of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Padraig J FlanneryDepartment of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Mrunal DehankarDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Cory C FunkInstitute for Systems Biology, Seattle, WA, 98109-5263, USA.ORCID http://orcid.org/0000-0002-5229-9011
Jordan WilkinsDepartment of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Anna StepanovaDivision of Neonatology, Department of Pediatrics, Columbia University, 116th St & Broadway, New York, NY, 10027, USA.
Tara O'HaganDivision of Neonatology, Department of Pediatrics, Columbia University, 116th St & Broadway, New York, NY, 10027, USA.
Alexander GalkinDivision of Neonatology, Department of Pediatrics, Columbia University, 116th St & Broadway, New York, NY, 10027, USA.ORCID http://orcid.org/0000-0001-8469-2283
Jarred NesbittDepartment of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Xiujuan ZhuDepartment of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Utkarsh TripathiDepartment of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Slobodan MacuraDepartment of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.ORCID http://orcid.org/0000-0002-6054-5163
Tamar TchkoniaRobert and Arlene Kogod Center on Aging, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.ORCID http://orcid.org/0000-0003-4623-7145
Tamar PirtskhalavaRobert and Arlene Kogod Center on Aging, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
James L KirklandRobert and Arlene Kogod Center on Aging, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.ORCID http://orcid.org/0000-0003-1676-4905
Rachel A KudgusDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Renee A SchoonDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Joel M ReidDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Yu YamazakiDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Takahisa KanekiyoDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.ORCID http://orcid.org/0000-0001-6751-9374
Song ZhangDepartment of Cardiovascular Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.ORCID http://orcid.org/0000-0002-9786-802X
Emirhan NemutluFaculty of Pharmacy, Department of Analytical Chemistry, Hacettepe University, Sihhiye, Ankara, 06100, Turkey.ORCID http://orcid.org/0000-0002-7337-6215
Petras DzejaDepartment of Cardiovascular Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Adam JaspersenMicroscopy and Cell Analysis Core, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Ye In Christopher KwonInstitute for Translational Neuroscience, University of Minnesota Twin Cities, 2101 6th Street SE, Minneapolis, MN, 55455, USA.
Michael K LeeInstitute for Translational Neuroscience, University of Minnesota Twin Cities, 2101 6th Street SE, Minneapolis, MN, 55455, USA.
Eugenia TrushinaDepartment of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA. trushina.eugenia@mayo.edu.ORCID http://orcid.org/0000-0002-6291-2860
Mayo Clinic · USColumbia University · USUniversity of Minnesota · USMayo Clinic in Florida · USHacettepe University · TRInstitute for Systems Biology · US
Funding
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3MTargeting Cellular Senescence to Extend HealthspanP01AG062413 · NIA · MAYO CLINIC ROCHESTER · PI Sundeep Khosla · 2019 to 2026
$28.7MMitochondrial Complex I as a Target for Neuroprotection in ADRF1AG055549 · NIA · MAYO CLINIC ROCHESTER · PI TRUSHINA, EUGENIA · 2017 to 2025
$7.0MEffect of Aging on Preadipocyte DifferentiationR37AG013925 · NIA · MAYO CLINIC ROCHESTER · PI KIRKLAND, JAMES L. · 2016 to 2025
$6.6MAMP-Kinase as a target for neuroprotection in ADRF1AG062135 · NIA · UNIVERSITY OF MINNESOTA · PI LEE, MICHAEL K, TRUSHINA, EUGENIA · 2019 to 2019
$3.2MSmall molecule mitochondria-targeted therapeutics for Huntingtons DiseaseR01NS107265 · NINDS · MAYO CLINIC ROCHESTER · PI TRUSHINA, EUGENIA · 2018 to 2021
$2.2MThe Role of FMN Loss by Mitochondrial Complex I in Neonatal Hypoxic-Ischemic Brain InjuryR01NS112381 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI GALKIN, ALEXANDER · 2020 to 2024
$2.1MAstrocytic function in DBS for essential tremorR01NS088260 · NINDS · MAYO CLINIC ROCHESTER · PI CHANG, SU-YOUNE · 2015 to 2019
$1.7MSmall Molecule Mitochondria-Targeted Therapeutics for AD (Supplement)UH3NS113776 · NINDS · MAYO CLINIC ROCHESTER · PI TRUSHINA, EUGENIA · 2022 to 2022
$1.1MMetabolic Origin of Oxidative Stress Injury in Brain Ischemia/ReperfusionR21NS125466 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI GALKIN, ALEXANDER, GROSS, STEVEN S · 2022 to 2023
$466kNCI NIH HHS P30 CA015083NIA NIH HHS P01 AG062413NIA NIH HHS R37 AG013925NIA NIH HHS RF1 AG055549NIA NIH HHS RF1 AG062135NINDS NIH HHS R01 NS088260NINDS NIH HHS R01 NS107265NINDS NIH HHS R01 NS112381NINDS NIH HHS R21 NS125466NINDS NIH HHS UH3 NS113776
Abstract
Alzheimer's Disease (AD) is a devastating neurodegenerative disorder without a cure. Here we show that mitochondrial respiratory chain complex I is an important small molecule druggable target in AD. Partial inhibition of complex I triggers the AMP-activated protein kinase-dependent signaling network leading to neuroprotection in symptomatic APP/PS1 female mice, a translational model of AD. Treatment of symptomatic APP/PS1 mice with complex I inhibitor improved energy homeostasis, synaptic activity, long-term potentiation, dendritic spine maturation, cognitive function and proteostasis, and reduced oxidative stress and inflammation in brain and periphery, ultimately blocking the ongoing neurodegeneration. Therapeutic efficacy in vivo was monitored using translational biomarkers FDG-PET,
Indexed as
Alzheimer DiseaseAnimalsBrainCognitionDisease Models, AnimalDrug Evaluation, PreclinicalElectron Transport Complex IFemaleMiceMice, Inbred C57BLMice, TransgenicNeuroprotectionProof of Concept StudyPyronesSignal TransductionCP2 compoundElectron Transport Complex IPyrones
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.