ArticleJCI insight2020
Role of defective calcium regulation in cardiorespiratory dysfunction in Huntington's disease.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Beyond the brain: Polyglutamine disease pathology outside the nervous system.Neurobiology of disease · 2026Review
- Integrated effects of altered action potentials and calcium release on skeletal muscle force generation in transgenic Huntington's disease mice.Pflugers Archiv : European journal of physiology · 2026Article
- Targeting ryanodine receptors with allopurinol and xanthine derivatives for the treatment of cardiac and musculoskeletal weakness disorders.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Dynamic dysregulation of transcriptomic networks in brainstem autonomic nuclei during hypertension development in the female spontaneously hypertensive rat.Physiological genomics · 2024Article
- Astroglial calcium signaling and homeostasis in tuberous sclerosis complex.Acta neuropathologica · 2024Article
- A Set of Possible Markers for Monitoring Heart Failure and Cognitive Impairment Associated: A Review of Literature from the Past 5 Years.Biomolecules · 2024Review
- Computer simulations predict the impact of neuronal atrophy on the calcium dynamics in Huntington's disease.PNAS nexus · 2024Article
- Aberrant mitochondrial dynamics contributes to diaphragmatic weakness induced by mechanical ventilation.PNAS nexus · 2023Article
- Defective cerebellar ryanodine receptor type 1 and endoplasmic reticulum calcium 'leak' in tremor pathophysiology.Acta neuropathologica · 2023Article
- Heart failure-induced cognitive dysfunction is mediated by intracellular CaNature neuroscience · 2023Article
- Targeting ryanodine receptors to treat human diseases.The Journal of clinical investigation · 2023Review
- Pain in Huntington's disease and its potential mechanisms.Frontiers in aging neuroscience · 2023Review
- Article
- Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment.Science advances · 2022Article
- Role of oxidation of excitation-contraction coupling machinery in age-dependent loss of muscle function ineLife · 2022Article
- Alzheimer's-like signaling in brains of COVID-19 patients.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- High-resolution structure of the membrane-embedded skeletal muscle ryanodine receptor.Structure (London, England : 1993) · 2022Article
- An Optogenetic Arrhythmia Model-Insertion of Several Catecholaminergic Polymorphic Ventricular Tachycardia Mutations IntoFrontiers in physiology · 2022Article
- RyR1-related myopathy mutations in ATP and calcium binding sites impair channel regulation.Acta neuropathologica communications · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder affecting striatal neurons beginning in young adults with loss of muscle coordination and cognitive decline. Less appreciated is the fact that patients with HD also exhibit cardiac and respiratory dysfunction, including pulmonary insufficiency and cardiac arrhythmias. The underlying mechanism for these symptoms is poorly understood. In the present study we provide insight into the cause of cardiorespiratory dysfunction in HD and identify a potentially novel therapeutic target. We now show that intracellular calcium (Ca2+) leak via posttranslationally modified ryanodine receptor/intracellular calcium release (RyR) channels plays an important role in HD pathology. RyR channels were oxidized, PKA phosphorylated, and leaky in brain, heart, and diaphragm both in patients with HD and in a murine model of HD (Q175). HD mice (Q175) with endoplasmic reticulum Ca2+ leak exhibited cognitive dysfunction, decreased parasympathetic tone associated with cardiac arrhythmias, and reduced diaphragmatic contractile function resulting in impaired respiratory function. Defects in cognitive, motor, and respiratory functions were ameliorated by treatment with a novel Rycal small-molecule drug (S107) that fixes leaky RyR. Thus, leaky RyRs likely play a role in neuronal, cardiac, and diaphragmatic pathophysiology in HD, and RyRs are a potential novel therapeutic target.
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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.