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Cited by 111Parkinson's Disease Mechanisms and TreatmentsNeurological diseases and metabolismIron Metabolism and Disorders

Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease

Hochstrasser, H., Bauer, P., Walter, U., Behnke, S., Spiegel, J., Csoti, I., Zeiler, B., Bornemann, A. +4 more·2004·Neurology
DOI 10.1212/01.wnl.0000144276.29988.c3
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Abstract

BACKGROUND: Transcranial ultrasound may be used to detect increased iron levels of the substantia nigra (SN) in patients with Parkinson disease (PD) and in control subjects. It is not known whether iron accumulation in PD is a primary or secondary phenomenon. However, sequence variations in genes involved in iron metabolism have been linked to basal ganglia disorders. One of these is ceruloplasmin (Cp), which is vitally involved in iron transport across the cell membrane. METHODS: One hundred seventy-six patients with PD according to the UK Brain Bank criteria and 180 ethnically matched control subjects, who were previously examined for SN iron signal changes by transcranial ultrasound, were examined for mutations in the Cp gene using denaturing high-performance liquid chromatography and subsequent sequencing for verification of unequivocal signals. Immunohistochemistry of PD midbrains was performed to examine the presence of Cp in Lewy bodies. RESULTS: Five novel missense variations were detected. One of these (I63T) was found in a single PD patient. A known variation (D554E) was significantly associated with PD and the ultrasound marker for increased SN iron levels. Moreover, a third sequence variation (R793H) was found to segregate with the ultrasound marker for increased iron levels in patients and control subjects. Immunohistochemistry demonstrated that Cp co-localizes with Lewy bodies in PD. CONCLUSIONS: Detection of sequence variations in a single Parkinson disease (PD) patient or associated with the ultrasound marker for increased substantia nigra iron levels and the presence of ceruloplasmin (Cp) immunoreactivity in Lewy bodies underline a suspected role for Cp in the pathogenesis of PD. Further functional analyses are warranted to investigate whether these variations are causally linked to the complex pathogenesis of PD in a subset of cases.

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  • Several missense variations in the gene encoding ceruloplasmin, which could affect the mobilisation of reactive iron, have been reported in a few patients with Parkinson's disease.

    “Several missense variations in the gene encoding ceruloplasmin, which could affect the mobilisation of reactive iron, have been reported in a few patients with Parkinson’s disease.137”

    From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [137]

  • DMT1 products include four different transcripts that occur as a result of alternative splicing at either the 3′ or 5′ end.

    “DMT1 products include four different transcripts that occur as a result of alternative splicing at either the 3′ or 5′ end.”

    From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [137]

  • DMT1A was regulated by iron in human Caco-2 cells, a model system for intestinal iron absorption.

    “DMT1A was regulated by iron in human Caco-2 cells, a model system for intestinal iron absorption (see Fig. 2) (137).”

    From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [137]

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Authors
Hochstrasser, H., Bauer, P., Walter, U., Behnke, S., Spiegel, J., Csoti, I., Zeiler, B., Bornemann, A., Pahnke, J., Becker, G., Riess, O., & Berg, D.
Affiliations
  • University of Zurich (CH)
  • From the Institutes for Medical Genetics (Drs. Bauer, Riess, and Berg, H. Hochstrasser) and Brain Research (Dr. Bornemann) and Hertie Institute for Brain Research (Dr. Berg), University of Tuebingen, Department of Neurology (Dr. Walter), University of Rostock, Department of Neurology (Drs. Behnke, Spiegel, and Zeiler), University of Homburg/Saar, and Gertrudis Parkinson Klinik (Dr. Csoti), Biskirchen, Germany; and Institute for Neuropathology (Dr. Pahnke), University of Zurich, Switzerland.
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2004-11-23
Volume
63
Issue
10
Pages
1912-1917
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/01.wnl.0000144276.29988.c3
OpenAlex
W2061399540
Cited by
111
References
35
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 1 · 2015: 7 · 2014: 7 · 2013: 6 · 2012: 6
FWCI
4.69
Type
journal article
Language
en
Open access
closed
Locations
  • Neurology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
Parkinson's disease, ceruloplasmin, substantia nigra hyperechogenicity, iron accumulation, transcranial ultrasound, genetic variants, missense mutations, Lewy bodies, iron metabolism, genetic susceptibility, pathogenesis
MeSH terms
Aged, Ceruloplasmin, Chromatography, High Pressure Liquid, DNA Mutational Analysis, Female, Humans, Iron, Male, Middle Aged, Parkinson Disease, Polymorphism, Restriction Fragment Length, Substantia Nigra, Genetic Variation, Lewy Bodies, Point Mutation, Ultrasonography, Doppler, Transcranial, Amino Acid Substitution, Mutation, Missense

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