Neuroprotection by iron chelator against proteasome inhibitor-induced nigral degeneration
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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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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