ArticleScientific reports2021
Pathologically phosphorylated tau at S396/404 (PHF-1) is accumulated inside of hippocampal synaptic mitochondria of aged Wild-type mice.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 81 citations in OpenAlex.
- Tau protein as a regulator of mitochondrial function and dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Impairment of hippocampal long-term potentiation by soluble amyloid-β oligomers is mediated by glutamate transporter 1 expressed in neurons.Neural regeneration research · 2026Article
- Synaptic mitochondria in aging and neurodegenerative diseases: Functional decline and vulnerability.Neural regeneration research · 2026Article
- Neuron-specific epigenetic repression ofbioRxiv : the preprint server for biology · 2026Article
- Early mitophagy activation by Urolithin A prevents, but late activation does not reverse, age-related cognitive impairment.npj aging · 2026Article
- Autophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC-Derived Cortical Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Adiponectin-PP2A Pathway Confers Cognitive Benefits of Physical Exercise Against Chronic Stress-Induced Tau Hyperphosphorylation in the Hippocampus.Aging cell · 2026Article
- A Review on the Pathophysiology of Alzheimer's Disease.Current protein & peptide science · 2026Review
- Synaptic mitochondrial dysfunction and Alzheimer's disease: from molecular mechanisms to therapeutic strategies.Frontiers in pharmacology · 2026Review
- Unraveling sex differences in age-related hippocampal decline: differential mitochondrial dysfunction, Lonp1-dependent mitochondrial proteostasis and mtROS production in aged C57BL/6 mice.Cell death & disease · 2025Article
- Mitochondrial dysfunction in cellular senescence: a bridge to neurodegenerative disease.npj aging · 2025Review
- Tau Protein Disrupts Mitochondrial Homeostasis in a Yeast Model: Implications for Alzheimer's Disease.Molecular neurobiology · 2025Article
- Tau-Mitochondria Interactions in Neurodegeneration: Mechanisms and Therapeutic Potential.Cellular and molecular neurobiology · 2025Review
- Identifying a novel Mecp2-mediated epigenetic mechanism controlling Lonp1 in the hippocampus and its disruption by aging.Scientific reports · 2025Article
- Dual inhibition of IRAK1/TAK1 signaling in astrocytes reduces accelerated mortality in human APOE4 knock-in APPswe/PSEN1dE9/P301S-Tau triple transgenic mouse model.Journal of neuroinflammation · 2025Article
- The absence of Parkin in hTau mice leads to synaptic mitochondrial dysfunction, alterations to the synaptic proteome, and increased phosphorylated tau in the Hippocampus.Neurobiology of disease · 2025Article
- Temporal Interactome Mapping of Human Tau in Drosophila Reveals Progressive Mitochondrial Engagement and Porin/VDAC1-Dependent Modulation of Toxicity.International journal of molecular sciences · 2025Article
- Fecal Microbiota Transplantation in Alzheimer's Disease: Mechanistic Insights Through the Microbiota-Gut-Brain Axis and Therapeutic Prospects.Microorganisms · 2025Review
- Looking into Abnormal Co-Expressions of Tau and TDP-43 in the Realm of Mixed Dementia Types: A Double-Punch Scenario.Brain sciences · 2025Review
- Differential roles of human tau isoforms in the modulation of inflammation and development of neuropathology.Neurobiology of disease · 2025Article
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4 authors at 1 institution in 1 country.
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Abstract
Brain aging is a natural process characterized by cognitive decline and memory loss. This impairment is related to mitochondrial dysfunction and has recently been linked to the accumulation of abnormal proteins in the hippocampus. Age-related mitochondrial dysfunction could be induced by modified forms of tau. Here, we demonstrated that phosphorylated tau at Ser 396/404 sites, epitope known as PHF-1, is increased in the hippocampus of aged mice at the same time that oxidative damage and mitochondrial dysfunction are observed. Most importantly, we showed that tau PHF-1 is located in hippocampal mitochondria and accumulates in the mitochondria of old mice. Finally, since two mitochondrial populations were found in neurons, we evaluated tau PHF-1 levels in both non-synaptic and synaptic mitochondria. Interestingly, our results revealed that tau PHF-1 accumulates primarily in synaptic mitochondria during aging, and immunogold electron microscopy and Proteinase K protection assays demonstrated that tau PHF-1 is located inside mitochondria. These results demonstrated the presence of phosphorylated tau at PHF-1 commonly related to tauopathy, inside the mitochondria from the hippocampus of healthy aged mice for the first time. Thus, this study strongly suggests that synaptic mitochondria could be damaged by tau PHF-1 accumulation inside this organelle, which in turn could result in synaptic mitochondrial dysfunction, contributing to synaptic failure and memory loss at an advanced age.
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