ArticleMolecular neurodegeneration2011
TRPM8 and Nav1.8 sodium channels are required for transthyretin-induced calcium influx in growth cones of small-diameter TrkA-positive sensory neurons.
Article in Molecular neurodegeneration, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Pharmacodynamic Effects of VX-150, a Highly Selective NaV1.8 Inhibitor, in Healthy Male Adults.Pain medicine (Malden, Mass.) · 2021Trial
- The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy.PloS one · 2015Trial
- Understanding animal temperature sensation: from molecular thermosensors to physiological impacts.Science China. Life sciences · 2026Review
- Ion Channels as Potential Drug Targets in Dry Eye Disease and Their Clinical Relevance: A Review.Cells · 2024Review
- Heterogenous electrophysiological features in early stage of hereditary transthyretin amyloidosis neuropathy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Quantitative Sensory Testing in Late-Onset ATTRv Presymptomatic Subjects: A Single Center Experience.Biomedicines · 2022Article
- The role of transthyretin in cell biology: impact on human pathophysiology.Cellular and molecular life sciences : CMLS · 2021Review
- Review
- Transthyretin interacts with actin regulators in a Drosophila model of familial amyloid polyneuropathy.Scientific reports · 2020Article
- Biochemical and Electrophysiological Modification of Amyloid Transthyretin on Cardiomyocytes.Biophysical journal · 2016Article
- Enzyme enhancers for the treatment of Fabry and Pompe disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Trafficking of ThermoTRP Channels.Membranes · 2014Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFamilial amyloidotic polyneuropathy (FAP) is a peripheral neuropathy caused by the extracellular accumulation and deposition of insoluble transthyretin (TTR) aggregates. However the molecular mechanism that underlies TTR toxicity in peripheral nerves is unclear. Previous studies have suggested that amyloidogenic proteins can aggregate into oligomers which disrupt intracellular calcium homeostasis by increasing the permeability of the plasma membrane to extracellular calcium. The aim of the present study was to examine the effect of TTR on calcium influx in dorsal root ganglion neurons.
resultsLevels of intracellular cytosolic calcium were monitored in dorsal root ganglion (DRG) neurons isolated from embryonic rats using the calcium-sensitive fluorescent indicator Fluo4. An amyloidogenic mutant form of TTR, L55P, induced calcium influx into the growth cones of DRG neurons, whereas wild-type TTR had no significant effect. Atomic force microscopy and dynamic light scattering studies confirmed that the L55P TTR contained oligomeric species of TTR. The effect of L55P TTR was decreased by blockers of voltage-gated calcium channels (VGCC), as well as by blockers of Nav1.8 voltage-gated sodium channels and transient receptor potential M8 (TRPM8) channels. siRNA knockdown of TRPM8 channels using three different TRPM8 siRNAs strongly inhibited calcium influx in DRG growth cones.
conclusionsThese data suggest that activation of TRPM8 channels triggers the activation of Nav1.8 channels which leads to calcium influx through VGCC. We suggest that TTR-induced calcium influx into DRG neurons may contribute to the pathophysiology of FAP. Furthermore, we speculate that similar mechanisms may mediate the toxic effects of other amyloidogenic proteins such as the β-amyloid protein of 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.