ArticleJournal of neurochemistry2014
A vesicular sequestration to oxidative deamination shift in myocardial sympathetic nerves in Parkinson's disease.
Article in Journal of neurochemistry, 2014. 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, 32 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
- 3,4-Dihydroxyphenylglycol levels separate multiple system atrophy from Parkinson disease with orthostatic hypotension.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2025Observational
- Pathophysiological Significance of α-Synuclein in Sympathetic Nerves: In Vivo Observations.Neurology · 2025Observational
- Modeling the Progression of Cardiac Catecholamine Deficiency in Lewy Body Diseases.Journal of the American Heart Association · 2022Article
- Sex-Specific Alterations in Dopamine Metabolism in the Brain after Methamphetamine Self-Administration.International journal of molecular sciences · 2022Article
- Pathophysiological significance of increased α-synuclein deposition in sympathetic nerves in Parkinson's disease: a post-mortem observational study.Translational neurodegeneration · 2022Observational
- Accuracy of Cardiac Innervation Scintigraphy for Mild Cognitive Impairment With Lewy Bodies.Neurology · 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
- "Sick-but-not-dead": multiple paths to catecholamine deficiency in Lewy body diseases.Stress (Amsterdam, Netherlands) · 2020Review
- The "Sick-but-not-Dead" Phenomenon Applied to Catecholamine Deficiency in Neurodegenerative Diseases.Seminars in neurology · 2020Review
- The catecholaldehyde hypothesis: where MAO fits in.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- Biofluid Markers for Prodromal Parkinson's Disease: Evidence From a Catecholaminergic Perspective.Frontiers in neurology · 2020Review
- Long-term trends in myocardial sympathetic innervation and function in synucleinopathies.Parkinsonism & related disorders · 2019Observational
- Computational modeling reveals multiple abnormalities of myocardial noradrenergic function in Lewy body diseases.JCI insight · 2019Article
- Alpha-Synuclein Deposition Within Sympathetic Noradrenergic Neurons Is Associated With Myocardial Noradrenergic Deficiency in Neurogenic Orthostatic Hypotension.Hypertension (Dallas, Tex. : 1979) · 2019Article
- The heart of PD: Lewy body diseases as neurocardiologic disorders.Brain research · 2019Review
- 3,4-Dihydroxyphenylacetaldehyde-Induced Protein Modifications and Their Mitigation byThe Journal of pharmacology and experimental therapeutics · 2018Article
- Linking Stress, Catecholamine Autotoxicity, and Allostatic Load with Neurodegenerative Diseases: A Focused Review in Memory of Richard Kvetnansky.Cellular and molecular neurobiology · 2018Review
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
In Parkinson's disease (PD), profound putamen dopamine (DA) depletion reflects denervation and a shift from vesicular sequestration to oxidative deamination of cytoplasmic DA in residual terminals. PD also involves cardiac sympathetic denervation. Whether PD entails myocardial norepinephrine (NE) depletion and a sequestration-deamination shift have been unknown. We measured apical myocardial tissue concentrations of NE, DA, and their neuronal metabolites 3,4-dihydroxyphenylglycol (DHPG), and 3,4-dihydroxyphenylacetic acid (DOPAC) from 23 PD patients and 23 controls and ascertained the extent of myocardial NE depletion in PD. We devised, validated in VMAT2-Lo mice, and applied 5 neurochemical indices of the sequestration-deamination shift-concentration ratios of DOPAC:DA, DA:NE, DHPG:NE, DOPAC:NE, and DHPG:DOPAC-and used a kinetic model to estimate the extent of the vesicular storage defect. The PD group had decreased myocardial NE content (p < 0.0001). The majority of patients (70%) had severe NE depletion (mean 2% of control), and in this subgroup all five indices of a sequestration-deamination shift were increased compared to controls (p < 0.001 for each). Vesicular storage in residual nerves was estimated to be decreased by 84-91% in this subgroup. We conclude that most PD patients have severe myocardial NE depletion, because of both sympathetic denervation and decreased vesicular storage in residual nerves. We found that the majority (70%) of Parkinson's disease (PD) patients have profound (98%) myocardial norepinephrine depletion, because of both cardiac sympathetic denervation and a shift from vesicular sequestration to oxidative deamination of cytoplasmic catecholamines in the residual nerves. This shift may be part of a final common pathogenetic pathway in the loss of catecholaminergic neurons that characterizes PD.
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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 Socratic graph.