ArticleProceedings of the National Academy of Sciences of the United States of America2008
Altered functional properties of a TRPM2 variant in Guamanian ALS and PD.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 123 citations in OpenAlex.
- CaCommunications biology · 2026Article
- Inhibiting the transient receptor potential melastatin 2 channel in microglia: current evidence and therapeutic potential in neurological disorders.Acta pharmacologica Sinica · 2026Review
- Development of Patient-Derived Neuroprogenitor Cells (hNPCs), Neurons and Astrocytes to Explore the Etiology of Guam Parkinsonism-Dementia Complex (PDC).bioRxiv : the preprint server for biology · 2025Article
- TRPM2-mediated feed-forward loop promotes chondrocyte damage in osteoarthritis via calcium-cGAS-STING-NF-κB pathway.Journal of advanced research · 2025Article
- Analysis of Transient Receptor Potential Ion Channels in ME/CFS.Methods in molecular biology (Clifton, N.J.) · 2025Article
- A conserved mechanism couples cytosolic domain movements to pore gating in the TRPM2 channel.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Combination of 5-FU and Resveratrol Can Suppress the Growth of Glioblastoma Cells Through Downregulation of TRPM2 and β-Catenin.Journal of molecular neuroscience : MN · 2024Article
- Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury.Frontiers in immunology · 2024Review
- The transient receptor potential melastatin 2: a new therapeutical target for Parkinson's disease?Neural regeneration research · 2023Review
- Functional characterization of the transient receptor potential melastatin 2 (TRPM2) cation channel from Nematostella vectensis reconstituted into lipid bilayer.Scientific reports · 2023Article
- Targeting TRP channels: recent advances in structure, ligand binding, and molecular mechanisms.Frontiers in molecular neuroscience · 2023Review
- Analysis of damage-associated molecular patterns in amyotrophic lateral sclerosis based on ScRNA-seq and bulk RNA-seq data.Frontiers in neuroscience · 2023Article
- Genetic Knockout of TRPM2 Increases Neuronal Excitability of Hippocampal Neurons by Inhibiting Kv7 Channel in Epilepsy.Molecular neurobiology · 2022Article
- Article
- The newest TRP channelopathy: Gain of function TRPM3 mutations cause epilepsy and intellectual disability.Channels (Austin, Tex.) · 2021Review
- TRP channels in health and disease at a glance.Journal of cell science · 2021Article
- Two Decades of Evolution of Our Understanding of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel.Life (Basel, Switzerland) · 2021Review
- Research progress on transient receptor potential melastatin 2 channel in nervous system diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Review
- Protective effect of transient receptor potential melastatin 2 inhibitor A10 on oxygen glucose deprivation/reperfusion model.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Article
- Functional Importance of Transient Receptor Potential (TRP) Channels in Neurological Disorders.Frontiers in cell and developmental biology · 2021Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 7 institutions in 1 country.
Funding
Abstract
Two related neurodegenerative disorders, Western Pacific amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD), originally occurred at a high incidence on Guam, in the Kii peninsula of Japan, and in southern West New Guinea more than 50 years ago. These three foci shared a unique mineral environment characterized by the presence of severely low levels of Ca(2+) and Mg(2+), coupled with high levels of bioavailable transition metals in the soil and drinking water. Epidemiological studies suggest that genetic factors also contribute to the etiology of these disorders. Here, we report that a variant of the transient receptor potential melastatin 2 (TRPM2) gene may confer susceptibility to these diseases. TRPM2 encodes a calcium-permeable cation channel highly expressed in the brain that has been implicated in mediating cell death induced by oxidants. We found a heterozygous variant of TRPM2 in a subset of Guamanian ALS (ALS-G) and PD (PD-G) cases. This variant, TRPM2(P1018L), produces a missense change in the channel protein whereby proline 1018 (Pro(1018)) is replaced by leucine (Leu(1018)). Functional studies revealed that, unlike WT TRPM2, P1018L channels inactivate. Our results suggest that the ability of TRPM2 to maintain sustained ion influx is a physiologically important function and that its disruption may, under certain conditions, contribute to disease states.
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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.