Evidence map›Paper›PMID 24945828›Full record

ReviewPharmacology & therapeutics2014

Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders.

David S Goldstein, Irwin J Kopin, Yehonatan Sharabi

Registry-linked trialAbstract readReview
In one paragraph

Review in Pharmacology & therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03104725 (Does N-Acetylcysteine Decrease Spontaneous Oxidation of Central Neural Dopamine in Parkinson's Disease?), which is not on this map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03104725 phase1terminatednot on this mapstarted 2017, after this paper: background citation

Does N-Acetylcysteine Decrease Spontaneous Oxidation of Central Neural Dopamine in Parkinson's Disease?

TypeinterventionalSponsorNational Institute of Neurological Disorders and Stroke (NINDS)Ran2017 to 2020Enrolled6ConditionsParkinson Disease, Cerebrospinal FluidArmsN-Acetylcysteine, Lumbar Puncture, Fluoroscopy
3 · Its place in the literature

Who cites it

89 citing papers in PubMed, 163 citations in OpenAlex.

  1. Suppression of pre-B cell colony formation by catecholamine oxidation.Journal of immunology (Baltimore, Md. : 1950) · 2026
    Article
  2. Preclinical Catecholaminergic Biomarkers of Central Lewy Body Diseases.Journal of clinical neurology (Seoul, Korea) · 2026
    Review
  3. Review
  4. Peripheral catecholamine systems: an evolutionary perspective.American journal of physiology. Regulatory, integrative and comparative physiology · 2025
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. A Potential Role for Neuroinflammation in ADHD.Advances in experimental medicine and biology · 2023
    Review
  17. Article
  18. Evidence-based complementary and alternative medicine : eCAM · 2023
    Article
  19. Review
  20. Article

29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

David S GoldsteinClinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: goldsteind@ninds.nih.gov.
Irwin J KopinClinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Yehonatan SharabiTel-Aviv University Sackler Faculty of Medicine, Tel-Aviv, Israel.
National Institute of Neurological Disorders and Stroke · USTel Aviv University · IL

Funding

Mechanisms of Parkinson Disease and Related DisordersZIANS003033 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI GOLDSTEIN, DAVID · 2009 to 2022
$8.2M
Treatment of Catecholaminergic NeurodegenerationZIANS003125 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI GOLDSTEIN, DAVID · 2011 to 2022
$3.2M
Intramural NIH HHS ZIA NS003033
6 · The paper itself

Abstract

Several neurodegenerative diseases involve loss of catecholamine neurons-Parkinson disease is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are vulnerable in PD and related disorders has been mysterious. Accumulating evidence supports the concept of "autotoxicity"-inherent cytotoxicity of catecholamines and their metabolites in the cells in which they are produced. According to the "catecholaldehyde hypothesis" for the pathogenesis of Parkinson disease, long-term increased build-up of 3,4-dihydroxyphenylacetaldehyde (DOPAL), the catecholaldehyde metabolite of dopamine, causes or contributes to the eventual death of dopaminergic neurons. Lewy bodies, a neuropathologic hallmark of PD, contain precipitated alpha-synuclein. Bases for the tendency of alpha-synuclein to precipitate in the cytoplasm of catecholaminergic neurons have also been mysterious. Since DOPAL potently oligomerizes and aggregates alpha-synuclein, the catecholaldehyde hypothesis provides a link between alpha-synucleinopathy and catecholamine neuron loss in Lewy body diseases. The concept developed here is that DOPAL and alpha-synuclein are nodes in a complex nexus of interacting homeostatic systems. Dysfunctions of several processes, including decreased vesicular sequestration of cytoplasmic catecholamines, decreased aldehyde dehydrogenase activity, and oligomerization of alpha-synuclein, lead to conversion from the stability afforded by negative feedback regulation to the instability, degeneration, and system failure caused by induction of positive feedback loops. These dysfunctions result from diverse combinations of genetic predispositions, environmental exposures, stress, and time. The notion of catecholamine autotoxicity has several implications for treatment, disease modification, and prevention. Conversely, disease modification clinical trials would provide key tests of the catecholaldehyde hypothesis.

Indexed as

3,4-Dihydroxyphenylacetic Acidalpha-SynucleinAnimalsApoptosisCatecholaminesHumansLipid PeroxidationNeurodegenerative DiseasesNeuronsOxidation-ReductionParkinson Disease3,4-dihydroxyphenylacetaldehyde3,4-Dihydroxyphenylacetic Acidalpha-SynucleinCatecholaminesAlpha-synucleinAutotoxicityCatecholamineDOPALParkinson disease

Identifiers

PMID24945828
PMCPMC4591072
OpenAlexW2060657561

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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.