ArticleJournal of molecular neuroscience : MN2019
Klotho Is Neuroprotective in the Superoxide Dismutase (SOD1
Article in Journal of molecular neuroscience : MN, 2019. 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, 45 citations in OpenAlex.
- Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases.Experimental physiology · 2026Review
- 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
- Caffeic Acid Phenethyl Ester Enhanced the Klotho/SIRT1/Nrf2/HO-1 Axis to Protect Against Methylmercury-Induced ALS-Like Neurodegeneration.Molecular neurobiology · 2026Article
- Association between serum alpha Klotho levels and the likelihood of abdominal aortic calcification.Scientific reports · 2026Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Klotho Deficiency Promotes Skeletal Muscle Weakness and Is Associated with Impaired Motor Unit Connectivity.International journal of molecular sciences · 2025Article
- MSCs engineered with secreted Klotho alleviate blood-brain barrier disruption and reduce neuroinflammation more effectively than MSCs in experimental autoimmune encephalomyelitis.Stem cell research & therapy · 2025Article
- Klotho deficiency promotes skeletal muscle weakness and is associated with impaired motor unit connectivity.bioRxiv : the preprint server for biology · 2025Article
- Klotho protein: a multifaceted regulator in aging and cancer dynamics.Molecular biology reports · 2025Review
- Sex-specific association between serum α-klotho levels and sleep disturbances in the elderly: a cross-sectional study.European journal of medical research · 2025Article
- Association between Klotho levels in cerebrospinal fluid and choroid plexus enlargement in neurodegeneration.Frontiers in aging neuroscience · 2025Article
- Article
- Enhanced Therapeutic Effects of Human Mesenchymal stem Cells Transduced with Secreted Klotho in a Murine Experimental Autoimmune Encephalomyelitis Model.Molecular neurobiology · 2024Article
- Klotho: molecular mechanisms and emerging therapeutics in central nervous system diseases.Molecular biology reports · 2024Review
- Knockout of the longevity gene Klotho perturbs aging and Alzheimer's disease-linked brain microRNAs and tRNA fragments.Communications biology · 2024Article
- [Research progress of metalloporphyrin against neurodegene-rative diseases].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Revisiting the mechanisms linking blood glucose to cognitive impairment: new evidence for the potential important role of klotho.Frontiers in endocrinology · 2024Article
- Artichoke (Cynara Scolymus) Methanolic Leaf Extract Alleviates Diethylnitrosamine-Induced Toxicity in BALB/c Mouse Brain: Involvement of Oxidative Stress and Apoptotically Related Klotho/PPARγ Signaling.Journal of personalized medicine · 2022Article
- Neuroprotective action of α-Klotho against LPS-activated glia conditioned medium in primary neuronal culture.Scientific reports · 2022Article
- Hemizygous Granzyme A Mice Expressing the hSOD1G93A Transgene Show Slightly Extended Lifespan.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of motor neurons in the brain and spinal cord. ALS neuropathology is associated with increased oxidative stress, excitotoxicity, and inflammation. We and others reported that the anti-aging and cognition-enhancing protein Klotho is a neuroprotective, antioxidative, anti-inflammatory, and promyelinating protein. In mice, its absence leads to an extremely shortened life span and to multiple phenotypes resembling human aging, including motor and hippocampal neurodegeneration and cognitive impairment. In contrast, its overexpression extends life span, enhances cognition, and confers resistance against oxidative stress; it also reduces premature mortality and cognitive and behavioral abnormalities in an animal model for Alzheimer's disease (AD). These pleiotropic beneficial properties of Klotho suggest that Klotho could be a potent therapeutic target for preventing neurodegeneration in ALS. Klotho overexpression in the SOD1 mouse model of ALS resulted in delayed onset and progression of the disease and extended survival that was more prominent in females than in males. Klotho reduced the expression of neuroinflammatory markers and prevented neuronal loss with the more profound effect in the spinal cord than in the motor cortex. The effect of Klotho was accompanied by reduced expression of proinflammatory cytokines and enhanced the expression of antioxidative and promyelinating factors in the motor cortex and spinal cord of Klotho × SOD1 compared to SOD1 mice. Our study provides evidence that increased levels of Klotho alleviate ALS-associated pathology in the SOD1 mouse model and may serve as a basis for developing Klotho-based therapeutic strategies for ALS.
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