Cited by 133Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeuroinflammation and Neurodegeneration Mechanisms

Could a loss of α‐synuclein function put dopaminergic neurons at risk?

Perez, Ruth G., Hastings, Teresa G.·2004·Journal of Neurochemistry

Abstract

The α‐synuclein gene is implicated in Parkinson's disease, the symptoms of which occur after a marked loss of substantia nigra dopamine neurons. While the function of α‐synuclein is not entirely elucidated, one function appears to be as a normal regulatory protein that can bind to and inhibit tyrosine hydroxylase, the rate‐limiting enzyme in dopamine synthesis. Soluble α‐synuclein levels may be diminished in Parkinson's disease substantia nigra dopamine neurons both by reduced expression and by α‐synuclein aggregation as Lewy bodies and Lewy neurites form. The loss of functional α‐synuclein may then result in dysregulation of tyrosine hydroxylase, dopamine transport and dopamine storage, resulting in excess cytosolic dopamine. Because dopamine and its metabolites are reactive molecules capable of generating highly reactive quinones and reactive oxygen species, a failure to package dopamine into vesicles could cause irreversible damage to cellular macromolecules and contribute to resultant neurotoxicity. This review focuses on how a loss of normal α‐synuclein function may contribute to the dopamine‐related loss of substantia nigra neurons during Parkinson's disease pathogenesis.

Integrity signals

Registry

Crossref · 10.1111/j.1471-4159.2004.02423.x

Cites

79 of 79 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Perez, R. G., & Hastings, T. G.
Affiliations
University of Pittsburgh (US)
Corresponding author
Perez, Ruth G.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2004-04-27
Volume
89
Issue
6
Pages
1318-1324
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W1550083773
Cited by
133
References
79
Citations by year
2026: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 9 · 2020: 6 · 2019: 2 · 2018: 5 · 2017: 8 · 2016: 7 · 2015: 3 · 2014: 1 · 2013: 8 · 2012: 12
FWCI
1.54
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Michael J. Fox Foundation for Parkinson's Research
  • National Institute on Drug Abuse (DA 09601)
  • National Institute of Neurological Disorders and Stroke (NS42094, R21NS045336, R01NS044076, R01NS042094, NS 44076)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
alpha-synuclein, Parkinson's disease, dopaminergic neurons, substantia nigra, tyrosine hydroxylase, dopamine synthesis, dopamine transport, dopamine storage, alpha-synuclein aggregation, Lewy bodies, Lewy neurites, reactive oxygen species, dopamine quinone, neurotoxicity
MeSH terms
Animals, Disease Models, Animal, Dopamine, Drosophila, Humans, Nerve Tissue Proteins, Neurons, Parkinson Disease, Tyrosine 3-Monooxygenase, Molecular Chaperones, Synucleins, alpha-Synuclein

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review