ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Arginine deprivation and immune suppression in a mouse model of Alzheimer's disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 178 citations in OpenAlex.
- Association of Serum Manganese Levels with Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.Nutrients · 2017Pooled it
- Nitric oxide-driven Warburg reprogramming at the NOS2-COX2 axis: An integrative engine of cancer hallmarks.Redox biology · 2026Review
- DEVELOPMENT AND APPLICATION OF BRAIN TISSUE BASED MULTI-OMICS PROFILE SCORES FOR ALZHEIMER'S DISEASE.Research square · 2026Article
- Cerebral Blood Flow Responses to Extracranial Alternating Current Brain Stimulation in CVN Mouse Model of Alzheimer's Disease: A Pilot Study Determining Optimal Dose.Neuromodulation : journal of the International Neuromodulation Society · 2026Article
- From metabolism to neurodegeneration: how microglial functional reprogramming drives neurodegenerative diseases.Frontiers in molecular neuroscience · 2026Review
- Acute liver failure-induced arginine deficiency impairs blood-brain barrier via inhibiting mTORC1-S6K1/4EBP1 pathway and inducing autophagy.Cell death & disease · 2025Article
- Nutrient sensing receptor GPRC6A regulates mTORC1 signaling and Tau biology.Neurobiology of disease · 2025Article
- Neuroimaging biomarkers of neuroprotection: Impact of voluntary versus enforced exercise in Alzheimer's disease models.Magnetic resonance imaging · 2025Article
- AA147 Alleviates Symptoms in a Mouse Model of Multiple Sclerosis by Reducing Oligodendrocyte Loss.Glia · 2025Article
- The Role of the Urea Cycle in the Alzheimer's Disease Brain.Journal of neurochemistry · 2025Review
- TMF Attenuates Cognitive Impairment and Neuroinflammation by Inhibiting the MAPK/NF-κB Pathway in Alzheimer's Disease: A Multi-Omics Analysis.Marine drugs · 2025Article
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- Identification and Validation of Potential Biomarkers and Therapeutic Targets of COVID-19-related Depression.Combinatorial chemistry & high throughput screening · 2025Article
- Fueling neurodegeneration: metabolic insights into microglia functions.Journal of neuroinflammation · 2024Review
- The Possible Neuroprotective Effect of Caffeic Acid on Cognitive Changes and Anxiety-Like Behavior Occurring in Young Rats Fed on High-Fat Diet and Exposed to Chronic Stress: Role of β-Catenin/GSK-3B Pathway.Journal of molecular neuroscience : MN · 2024Article
- L-arginine metabolism ameliorates age-related cognitive impairment by Amuc_1100-mediated gut homeostasis maintaining.Aging cell · 2024Article
- Possible Role of Cellular Polyamine Metabolism in Neuronal Apoptosis.Current medical science · 2024Article
- Taming microglia: the promise of engineered microglia in treating neurological diseases.Journal of neuroinflammation · 2024Review
- Microfluidic models of the neurovascular unit: a translational view.Fluids and barriers of the CNS · 2023Review
- Mechanism of action deconvolution of the small-molecule pathological tau aggregation inhibitor Anle138b.Alzheimer's research & therapy · 2023Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The pathogenesis of Alzheimer's disease (AD) is a critical unsolved question; and although recent studies have demonstrated a strong association between altered brain immune responses and disease progression, the mechanistic cause of neuronal dysfunction and death is unknown. We have previously described the unique CVN-AD mouse model of AD, in which immune-mediated nitric oxide is lowered to mimic human levels, resulting in a mouse model that demonstrates the cardinal features of AD, including amyloid deposition, hyperphosphorylated and aggregated tau, behavioral changes, and age-dependent hippocampal neuronal loss. Using this mouse model, we studied longitudinal changes in brain immunity in relation to neuronal loss and, contrary to the predominant view that AD pathology is driven by proinflammatory factors, we find that the pathology in CVN-AD mice is driven by local immune suppression. Areas of hippocampal neuronal death are associated with the presence of immunosuppressive CD11c(+) microglia and extracellular arginase, resulting in arginine catabolism and reduced levels of total brain arginine. Pharmacologic disruption of the arginine utilization pathway by an inhibitor of arginase and ornithine decarboxylase protected the mice from AD-like pathology and significantly decreased CD11c expression. Our findings strongly implicate local immune-mediated amino acid catabolism as a novel and potentially critical mechanism mediating the age-dependent and regional loss of neurons in humans with 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 OpenQuestion graph.