ArticleThe Journal of clinical investigation2021
Aberrant AZIN2 and polyamine metabolism precipitates tau neuropathology.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Residue-Specific Modulation of Aggregation-Associated Interactions by Spermine in Tau, α‑Synuclein, and Aβ40.JACS Au · 2026Article
- Review
- Polyamine Metabolism in Brain Health and Disease.Neuropharmacology and therapy · 2026Article
- Residue-Specific Modulation of Aggregation-Associated Interactions by Spermine in Tau, α-Synuclein, and Aβ40.bioRxiv : the preprint server for biology · 2025Article
- Spermine modulation of Alzheimer's Tau and Parkinson's α-synuclein: implications for biomolecular condensation and neurodegeneration.Nature communications · 2025Article
- Nutrient sensing receptor GPRC6A regulates mTORC1 signaling and Tau biology.Neurobiology of disease · 2025Article
- Polyamination with spermidine enhances pathogenic tau conformations while reducing filamentous aggregate formation in vitro.The Biochemical journal · 2025Article
- Ornithine decarboxylase antizyme 2 (OAZ2) in human colon adenocarcinoma: a potent prognostic factor associated with immunity.Scientific reports · 2025Article
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- Comparative brain metabolomics reveals shared and distinct metabolic alterations in Alzheimer's disease and progressive supranuclear palsy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Tau accumulation is cleared by the induced expression of VCP via autophagy.Acta neuropathologica · 2024Article
- Non-Linear Association of Dietary Polyamines with the Risk of Incident Dementia: Results from Population-Based Cohort of the UK Biobank.Nutrients · 2024Article
- Unveiling the hidden players: noncoding RNAs orchestrating polyamine metabolism in disease.Cell & bioscience · 2024Review
- Reduction of spermine synthase enhances autophagy to suppress Tau accumulation.Cell death & disease · 2024Article
- Association of spermidine blood levels with microstructure of sleep-implications from a population-based study.GeroScience · 2024Article
- Dysregulation ofCurrent Alzheimer research · 2024Article
- Polyamine Dysregulation and Nucleolar Disruption in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- Polyamines: Key Players in Immunometabolism and Immune Regulation.Journal of cellular immunology · 2024Article
- The Molecular Role of Polyamines in Age-Related Diseases: An Update.International journal of molecular sciences · 2023Review
- Genetic Mapping of Behavioral Traits Using the Collaborative Cross Resource.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Tauopathies display a spectrum of phenotypes from cognitive to affective behavioral impairments; however, mechanisms promoting tau pathology and how tau elicits behavioral impairment remain unclear. We report a unique interaction between polyamine metabolism, behavioral impairment, and tau fate. Polyamines are ubiquitous aliphatic molecules that support neuronal function, axonal integrity, and cognitive processing. Transient increases in polyamine metabolism hallmark the cell's response to various insults, known as the polyamine stress response (PSR). Dysregulation of gene transcripts associated with polyamine metabolism in Alzheimer's disease (AD) brains were observed, and we found that ornithine decarboxylase antizyme inhibitor 2 (AZIN2) increased to the greatest extent. We showed that sustained AZIN2 overexpression elicited a maladaptive PSR in mice with underlying tauopathy (MAPT P301S; PS19). AZIN2 also increased acetylpolyamines, augmented tau deposition, and promoted cognitive and affective behavioral impairments. Higher-order polyamines displaced microtubule-associated tau to facilitate polymerization but also decreased tau seeding and oligomerization. Conversely, acetylpolyamines promoted tau seeding and oligomers. These data suggest that tauopathies launch an altered enzymatic signature that endorses a feed-forward cycle of disease progression. Taken together, the tau-induced PSR affects behavior and disease continuance, but may also position the polyamine pathway as a potential entry point for plausible targets and treatments of tauopathy, including AD.
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Registered trials
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 Socratic graph.