ArticlePloS one2011
The cycad genotoxin MAM modulates brain cellular pathways involved in neurodegenerative disease and cancer in a DNA damage-linked manner.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 68 citations in OpenAlex.
- Plant-Derived Anti-Cancer Therapeutics and Biopharmaceuticals.Bioengineering (Basel, Switzerland) · 2024Review
- Linking Environmental Genotoxins to Neurodegenerative Diseases Through Transcriptional Mutagenesis.International journal of molecular sciences · 2024Review
- Accidental Encounter of Repair Intermediates in Alkylated DNA May Lead to Double-Strand Breaks in Resting Cells.International journal of molecular sciences · 2024Review
- Introducing the Role of Genotoxicity in Neurodegenerative Diseases and Neuropsychiatric Disorders.International journal of molecular sciences · 2024Review
- Novel Techniques for Mapping DNA Damage and Repair in the Brain.International journal of molecular sciences · 2024Review
- Corrected speciation and gyromitrin content of false morels linked to ALS patients with mostly slow-acetylator phenotypes.eNeurologicalSci · 2024Article
- Reply to: Questioning the cycad theory of Kii ALS-PDC causation.Nature reviews. Neurology · 2024Article
- The cycad genotoxin methylazoxymethanol, linked to Guam ALS/PDC, induces transcriptional mutagenesis.Acta neuropathologica communications · 2024Article
- Neuropathological Examination of Mice Chronically Exposed to Secondhand Smoke.Military medicine · 2023Article
- Early-onset, conjugal, twin-discordant, and clusters of sporadic ALS: Pathway to discovery of etiologyFrontiers in neuroscience · 2023Review
- Association ofFrontiers in aging neuroscience · 2023Article
- Food-Borne Chemical Carcinogens and the Evidence for Human Cancer Risk.Foods (Basel, Switzerland) · 2022Review
- Nodding syndrome: A key role for sources of nutrition?eNeurologicalSci · 2022Review
- Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2022Review
- Article
- DNA damage as a mechanism of neurodegeneration in ALS and a contributor to astrocyte toxicity.Cellular and molecular life sciences : CMLS · 2021Review
- Mitochondria Endoplasmic Reticulum Contact Sites (MERCs): Proximity Ligation Assay as a Tool to Study Organelle Interaction.Frontiers in cell and developmental biology · 2021Review
- Genotoxic Damage During Brain Development Presages Prototypical Neurodegenerative Disease.Frontiers in neuroscience · 2021Review
- Plant and Fungal Hepatotoxicities of Cattle in Australia, with a Focus on Minimally Understood Toxins.Toxins · 2020Review
- Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of adult C57BL6 wild-type mice treated with a single systemic dose of MAM acetate display DNA damage (O⁶-methyldeoxyguanosine lesions, O⁶-mG) that remains constant up to 7 days post-treatment. By contrast, MAM-treated mice lacking a functional gene encoding the DNA repair enzyme O⁶-mG DNA methyltransferase (MGMT) showed elevated O⁶-mG DNA damage starting at 48 hours post-treatment. The DNA damage was linked to changes in the expression of genes in cell-signaling pathways associated with cancer, human neurodegenerative disease, and neurodevelopmental disorders. These data are consistent with the established developmental neurotoxic and carcinogenic properties of MAM in rodents. They also support the hypothesis that early-life exposure to MAM-glucoside (cycasin) has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for food or medicine, or both. These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer) or not (neurodegeneration). Exposure to MAM-related environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer's disease.
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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.