ArticleJCI insight2019
Computational modeling reveals multiple abnormalities of myocardial noradrenergic function in Lewy body diseases.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Catecholamine metabolism revisited: from neurochemistry to integrative physiology and pathophysiology.Physiological reviews · 2026Review
- Putamen dopamine synthesis, vesicular storage, and metabolism in Parkinson disease.medRxiv : the preprint server for health sciences · 2026Article
- Preclinical Catecholaminergic Biomarkers of Central Lewy Body Diseases.Journal of clinical neurology (Seoul, Korea) · 2026Review
- Multitracer PET to Assess Cardiac Sympathetic Innervation and Vesicular Storage in Lewy Body Diseases.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Peripheral catecholamine systems: an evolutionary perspective.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Review
- Decreased urinary excretion of norepinephrine and dopamine in autonomic synucleinopathies.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2025Article
- Novel F-18-labeled Tracers of Sympathetic Function for Improved Risk Stratification and Clinical Outcomes.Current cardiology reports · 2025Review
- Linking the Extended Autonomic System with the Homeostat Theory: New Perspectives about Dysautonomias.Journal of personalized medicine · 2024Article
- Cardiac noradrenergic deficiency revealed by 18F-dopamine positron emission tomography identifies preclinical central Lewy body diseases.The Journal of clinical investigation · 2024Article
- Dihydroxyphenylacetaldehyde Lowering Treatment Improves Locomotor and Neurochemical Abnormalities in the Rat Rotenone Model: Relevance to the Catecholaldehyde Hypothesis for the Pathogenesis of Parkinson's Disease.International journal of molecular sciences · 2023Article
- AJ76 and UH232 as potential agents for diagnosing early-stage Parkinson's disease.Neuropharmacology · 2023Article
- Modeling the Progression of Cardiac Catecholamine Deficiency in Lewy Body Diseases.Journal of the American Heart Association · 2022Article
- Pathophysiological significance of increased α-synuclein deposition in sympathetic nerves in Parkinson's disease: a post-mortem observational study.Translational neurodegeneration · 2022Observational
- The rat rotenone model reproduces the abnormal pattern of central catecholamine metabolism found in Parkinson's disease.Disease models & mechanisms · 2022Article
- Dynamic planar scintigraphy for the rapid kinetic measurement of myocardialEJNMMI research · 2021Article
- Differential Susceptibilities of Catecholamines to Metabolism by Monoamine Oxidases.The Journal of pharmacology and experimental therapeutics · 2021Article
- Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys.Scientific reports · 2021Article
- The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know.International journal of molecular sciences · 2021Review
- Cardioselective peripheral noradrenergic deficiency in Lewy body synucleinopathies.Annals of clinical and translational neurology · 2020Article
- "Sick-but-not-dead": multiple paths to catecholamine deficiency in Lewy body diseases.Stress (Amsterdam, Netherlands) · 2020Review
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Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundLewy body diseases, a family of aging-related neurodegenerative disorders, entail loss of the catecholamine dopamine in the nigrostriatal system and equally severe deficiency of the closely related catecholamine norepinephrine in the heart. The myocardial noradrenergic lesion is associated with major non-motor symptoms and decreased survival. Numerous mechanisms determine norepinephrine stores, and which of these are altered in Lewy body diseases has not been examined in an integrated way. We used a computational modeling approach to assess comprehensively pathways of cardiac norepinephrine synthesis, storage, release, reuptake, and metabolism in Lewy body diseases. Application of a novel kinetic model identified a pattern of dysfunctional steps contributing to norepinephrine deficiency. We then tested predictions from the model in a new cohort of Parkinson disease patients.
methodsRate constants were calculated for 17 reactions determining intra-neuronal norepinephrine stores. Model predictions were tested by measuring post-mortem apical ventricular concentrations and concentration ratios of catechols in controls and patients with Parkinson disease.
resultsThe model identified low rate constants for three types of processes in the Lewy body group-catecholamine biosynthesis via tyrosine hydroxylase and L-aromatic-amino-acid decarboxylase, vesicular storage of dopamine and norepinephrine, and neuronal norepinephrine reuptake via the cell membrane norepinephrine transporter. Post-mortem catechols and catechol ratios confirmed this triad of model-predicted functional abnormalities.
conclusionDenervation-independent impairments of neurotransmitter biosynthesis, vesicular sequestration, and norepinephrine recycling contribute to the myocardial norepinephrine deficiency attending Lewy body diseases. A proportion of cardiac sympathetic nerves are "sick but not dead," suggesting targeted disease-modification strategies might retard clinical progression.
trial registrationThis study was not a clinical trial.
fundingThe research reported here was supported by the Division of Intramural Research, NINDS.
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