Cited by 88Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeurological diseases and metabolism

Neuroprotection by iron chelator against proteasome inhibitor-induced nigral degeneration

Zhang, Xiong, Xie, Wenjie, Qu, Shen, Pan, Tianhong, Wang, Xiaotong, Le, Weidong·2005·Biochemical and Biophysical Research Communications

Abstract

The cause of the neurodegenerative process in Parkinson's disease (PD) remains unclear, but evidence suggests that failure of the ubiquitin-proteasome system may play a major role in the pathogenesis of the disease. Iron is believed to be a key contributor to PD pathology by inducing aggregation of alpha-synuclein and by generating oxidative stress. Our present studies have shown that micro-injection of the proteasome inhibitor lactacystin into the substantia nigra (SN) of C57BL/6 mice causes significant loss of dopaminergic cells and induces intracellular inclusion body formation. We have also found that co-injection of the iron chelator desferrioxamine not only attenuates the lactacystin-induced dopamine neuron loss, but also reduces the presence of ubiquitin-positive intracellular inclusions in the SN, whereas use of iron-deficient diet has no such protective effects. These results may support that iron plays a key role in proteasome inhibitor-induced nigral pathology and that reducing iron reactivity may prevent dopaminergic neuron degeneration and reduce abnormal protein aggregation.

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Crossref · 10.1016/j.bbrc.2005.05.150

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  • Iron-dependent oxidative stress induces depletion of antioxidants in the brain.

    “accumulating evidence has demonstrated that iron-dependent oxidative stress induces depletion of antioxidants in the brain [54,55].”

    From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [54]

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Authors
Zhang, X., Xie, W., Qu, S., Pan, T., Wang, X., & Le, W.
Affiliations
  • Baylor College of Medicine (US)
  • Wenzhou Medical University (CN)
Corresponding author
Le, Weidong
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2005-07
Volume
333
Issue
2
Pages
544-549
ISSN
0006-291X (ISSN-L)
OpenAlex
W2032539115
Cited by
87
References
24
Citations by year
2026: 1 · 2025: 1 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 5 · 2014: 1 · 2013: 6 · 2012: 5
FWCI
6.91
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (NINDS 043567, NINDS 40370)
  • National Institute of Neurological Disorders and Stroke (R01NS043567, R01NS040370)
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 › Neurological diseases and metabolism
Keywords
Parkinson's disease, neuroprotection, iron chelation, deferoxamine, lactacystin, proteasome inhibitors, substantia nigra, dopaminergic neuron loss, ubiquitin-proteasome system, alpha-synuclein aggregation, oxidative stress, iron deficiency diet, intracellular inclusions
MeSH terms
Acetylcysteine, Animals, Deferoxamine, Iron Chelating Agents, Male, Mice, Inbred C57BL, Nerve Degeneration, Substantia Nigra, Treatment Outcome, Neuroprotective Agents, Parkinsonian Disorders, Ubiquitin, Mice, Proteasome Inhibitors

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