ArticleThe Journal of biological chemistry2014
The neuroprotective effect of Klotho is mediated via regulation of members of the redox system.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 220 citations in OpenAlex.
- Trial
- Bone transcriptomics reveals that juzentaihoto remodels and activates multiple pathways in Klotho-deficient mice.Bone reports · 2026Article
- Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases.Experimental physiology · 2026Review
- α-Klotho as a central integrative signalling hub in cognitive function and neuroprotection in neurodegenerative diseases.Metabolic brain disease · 2026Review
- Gene deletion of Klotho in the dentate gyrus does not affect the number of adult-born granule cells.Scientific reports · 2026Article
- Converging neurotrophic-immune signaling in autism spectrum disorder: integrative roles of klotho, GDNF/GFRA-1, IGF-1 and GLP-1 pathways.Metabolic brain disease · 2026Review
- Humanized Klotho haplotypes cause widespread transcriptomic changes in mouse brain.bioRxiv : the preprint server for biology · 2026Article
- Elevated plasma klotho levels attenuate Alzheimer's disease pathologies and cognitive decline in APOE ε4 carriers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Klotho Function in Neurogenesis and Oligodendrogenesis: A Mini-Review Update.Journal of molecular neuroscience : MN · 2026Review
- Association between the serum Klotho levels and diabetic kidney disease: results from the NHANES 2007-2016 and Mendelian randomization study.Journal of diabetes and metabolic disorders · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Comparative Effects of Co-administration of Lactobacillus casei and Bifidobacterium breve vs. Monotherapy on Hippocampal Neurodegeneration in a D-Galactose-Induced Aging Model.Molecular neurobiology · 2025Article
- The Anti-Inflammatory Actions of Soluble Klotho in Brain Aging and Its Main Associated Diseases.International journal of molecular sciences · 2025Review
- Non-Skeletal Roles of Vitamin D in Skin, Gut, and Cardiovascular Disease: Focus on Epithelial Barrier Function and Immune Regulation in Chronic Disease.International journal of molecular sciences · 2025Review
- Klotho mediates the association between serum testosterone and severe abdominal aortic calcification: a cross-sectional study from the NHANES database.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Aerobic exercise-induced changes in fluid biomarkers in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Associations between klotho levels and mortality risk among middle-aged and older adults taking prescription opioids.Preventive medicine reports · 2025Article
- Sex-specific association between serum α-klotho levels and sleep disturbances in the elderly: a cross-sectional study.European journal of medical research · 2025Article
- Associations of KLOTHO-VS heterozygosity and α-Klotho protein with cerebrospinal fluid Alzheimer's disease biomarkers.Journal of Alzheimer's disease : JAD · 2025Article
- Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity.Molecular brain · 2025Article
70 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Generation of reactive oxygen species (ROS), leading to oxidative damage and neuronal cell death, plays an important role in the pathogenesis of neurodegenerative disorders, including Alzheimer disease. The present study aimed to examine the mechanism by which the anti-aging protein Klotho exerts neuroprotective effects against neuronal damage associated with neurodegeneration and oxidative stress. Pretreatment of rat primary hippocampal neurons and mouse hippocampal neuronal cell line HT22 with recombinant Klotho protected these cells from glutamate and oligomeric amyloid β (oAβ)-induced cytotoxicity. In addition, primary hippocampal neurons obtained from Klotho-overexpressing mouse embryos were more resistant to both cytotoxic insults, glutamate and oAβ, compared with neurons from wild-type littermates. An antioxidative stress array analysis of neurons treated with Klotho revealed that Klotho significantly enhances the expression of the thioredoxin/peroxiredoxin (Trx/Prx) system with the greatest effect on the induction of Prx-2, an antioxidant enzyme, whose increase was confirmed at the mRNA and protein levels. Klotho-induced phosphorylation of the PI3K/Akt pathway, a pathway important in apoptosis and longevity, was associated with sustained inhibitory phosphorylation of the transcription factor forkhead box O3a (FoxO3a) and was essential for the induction of Prx-2. Down-regulation of Prx-2 expression using a lentivirus harboring shRNA almost completely abolished the ability of Klotho to rescue neurons from glutamate-induced death and significantly, but not completely, inhibited cell death mediated by oAβ, suggesting that Prx-2 is a key modulator of neuroprotection. Thus, our results demonstrate, for the first time, the neuroprotective role of Klotho and reveal a novel mechanism underlying this effect.
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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 OpenQuestion graph.