ReviewAging2021
Alzheimer's disease as a chronic maladaptive polyamine stress response.
Review in Aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 52 citations in OpenAlex.
- A phase 2, randomized, multicenter, double-blind, placebo-controlled trial of S-adenosyl methionine in participants with mild cognitive impairment or dementia due to Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Trial
- High Plasma Polyamine Levels Are Associated With an Increased Risk of Poststroke Cognitive Impairment: A Multicenter Prospective Study From CATIS.Journal of the American Heart Association · 2025Trial
- Polyamine metabolic enzyme SAT1 remodels the neuronal transcriptome and rescues α-synuclein toxicity in Drosophila.Amino acids · 2026Article
- ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis.Nature communications · 2026Article
- Polyamines in CNS malignancies: positively charged culprits in the hijacking of neural and immune signaling pathways.Amino acids · 2026Review
- Sequential co-extraction of gut microbial DNA and fecal polyamines enables integrated microbiome-metabolite profiling in an Alzheimer's disease mouse model.Scientific reports · 2026Article
- Longitudinal metabolomic profiling of biogenic amines in plasma and CSF, and their correlation, reveals sex-specific and age changes in TgF344 Alzheimer's disease transgenic and wildtype rats.Fluids and barriers of the CNS · 2026Article
- Polyamine metabolic enzyme SAT1 remodels the neuronal transcriptome and rescues α-synuclein toxicity in Drosophila.Research square · 2026Article
- Unbiased distance correlation with sample-size-aware confidence bounds for comparative omics network analysis.Frontiers in bioinformatics · 2026Article
- Immunometabolic reprogramming of central and peripheral immune cells in mental disorders: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Age-Dependent Redistribution of the Life-Important Enzyme in the Retina: Adult Müller Glial Cells' Endfeet Lack Spermine Synthase Expression.Biomolecules · 2025Article
- Article
- Molecular basis of TRPV3 channel blockade by intracellular polyamines.Communications biology · 2025Article
- Polyamine biosynthesis dysregulation in Alzheimer's disease and Down syndrome cellular models.bioRxiv : the preprint server for biology · 2025Article
- Article
- Assessing the Role of Polyamine Metabolites in Blood and the DNA Methylation ofInternational journal of medical sciences · 2025Article
- Article
- Altered Arginine/Agmatine Pathway and Polyamines in Adolescents Diagnosed with Major Depressive Disorder.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2024Article
- Spermidine Synthase Localization in Retinal Layers: Early Age Changes.International journal of molecular sciences · 2024Article
- Reduction of spermine synthase enhances autophagy to suppress Tau accumulation.Cell death & disease · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polyamines are nitrogen-rich polycationic ubiquitous bioactive molecules with diverse evolutionary-conserved functions. Their activity interferes with numerous genes' expression resulting in cell proliferation and signaling modulation. The intracellular levels of polyamines are precisely controlled by an evolutionary-conserved machinery. Their transient synthesis is induced by heat stress, radiation, and other traumatic stimuli in a process termed the polyamine stress response (PSR). Notably, polyamine levels decline gradually with age; and external supplementation improves lifespan in model organisms. This corresponds to cytoprotective and reactive oxygen species scavenging properties of polyamines. Paradoxically, age-associated neurodegenerative disorders are characterized by upsurge in polyamines levels, indicating polyamine pleiotropic, adaptive, and pathogenic roles. Specifically, arginase overactivation and arginine brain deprivation have been shown to play an important role in Alzheimer's disease (AD) pathogenesis. Here, we assert that a universal short-term PSR associated with acute stimuli is beneficial for survival. However, it becomes detrimental and maladaptive following chronic noxious stimuli, especially in an aging organism. Furthermore, we regard cellular senescence as an adaptive response to stress and suggest that PSR plays a central role in age-related neurodegenerative diseases' pathogenesis. Our perspective on AD proposes an inclusive reassessment of the causal relationships between the classical hallmarks and clinical manifestation. Consequently, we offer a novel treatment strategy predicated upon this view and suggest fine-tuning of arginase activity with natural inhibitors to preclude or halt the development of AD-related dementia.
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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 Socratic graph.