ArticleJournal of neuroinflammation2022
Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer's disease mouse model.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 95 citations in OpenAlex.
- Trial
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Dysregulated polyamine metabolism in neurological disorders: molecular mechanisms and therapeutic opportunities.Molecular biology reports · 2026Review
- Cerebral Intramural Cells: A Missing Cellular Link Between Vascular Aging and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- The mitophagy-inflammasome axis: a shared pathological hub in Alzheimer's and Parkinson's diseases.Translational neurodegeneration · 2026Review
- Article
- Autophagy in Alzheimer's Disease: Mechanisms, Clinical Trials, and Horizons.Neuro-degenerative diseases · 2026Review
- Spermine suppressesmBio · 2026Article
- Hierarchical microtopology and phase-specific delivery functionally restore ultralong nerve continuity across species.Science advances · 2026Article
- The roles of microglia and astrocytes in inflammasomes and neurological disorders.Neural regeneration research · 2026Article
- Mitochondrial Dysfunction in Alzheimer's Disease and Mitochondria-Targeted Therapeutics.Cells · 2026Review
- Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Short-Term Oral Spermidine Supplementation Modifies Aspects of Neurodegenerative Disease in Flies and Mice With MPS III.Journal of inherited metabolic disease · 2026Article
- 4-Hydroxybenzyl Alcohol Mitigates Hyperlipidemia-Associated Depression by Inhibiting Neuroinflammation via the NKIRAS2/NF-κB Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Autophagy-Neuroinflammation Axis in Neurodegenerative Diseases: Mechanisms and Therapeutic Potential.Cells · 2026Review
- Spermidine in the aging brain: mechanisms, preclinical evidence, and clinical perspectives.Molecular biology reports · 2026Review
- Spermidine Attenuates Neuroimmune Dysfunction in Gulf War Illness via Modulation of the Gut- Brain Axis.Molecular neurobiology · 2026Article
- Transcriptomic Analysis Reveals the Beneficial Effects of Spermidine in an ALS Mouse Model.Biomolecules · 2026Article
- Spermidine Suppresses Peripheral Inflammation and Alleviates Non-Motor Symptoms in the 6-OHDA-Induced Rat Model of Parkinson's Disease.Molecules (Basel, Switzerland) · 2026Article
- The NLRP3 Inflammasome in Neuropsychiatric Disorders: Molecular Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDeposition of amyloid beta (Aβ) and hyperphosphorylated tau along with glial cell-mediated neuroinflammation are prominent pathogenic hallmarks of Alzheimer's disease (AD). In recent years, impairment of autophagy has been identified as another important feature contributing to AD progression. Therefore, the potential of the autophagy activator spermidine, a small body-endogenous polyamine often used as dietary supplement, was assessed on Aβ pathology and glial cell-mediated neuroinflammation.
resultsOral treatment of the amyloid prone AD-like APPPS1 mice with spermidine reduced neurotoxic soluble Aβ and decreased AD-associated neuroinflammation. Mechanistically, single nuclei sequencing revealed AD-associated microglia to be the main target of spermidine. This microglia population was characterized by increased AXL levels and expression of genes implicated in cell migration and phagocytosis. A subsequent proteome analysis of isolated microglia confirmed the anti-inflammatory and cytoskeletal effects of spermidine in APPPS1 mice. In primary microglia and astrocytes, spermidine-induced autophagy subsequently affected TLR3- and TLR4-mediated inflammatory processes, phagocytosis of Aβ and motility. Interestingly, spermidine regulated the neuroinflammatory response of microglia beyond transcriptional control by interfering with the assembly of the inflammasome.
conclusionsOur data highlight that the autophagy activator spermidine holds the potential to enhance Aβ degradation and to counteract glia-mediated neuroinflammation in AD pathology.
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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 OpenQuestion graph.