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The role of iron imaging in Huntington's disease
Simon J A van den Bogaard1, Eve M Dumas, Raymund A C Roos
1Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
Insights
Iron accumulation is observed in the brains of Huntington's disease (HD) patients, but evidence suggests it may not initiate the disease. Further research is needed to clarify iron's role in HD pathology.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the Htt gene.
- Iron dysregulation and oxidative stress are implicated in HD pathology, but their precise role remains unclear.
Purpose of the Study:
- To review the role of iron in Huntington's disease pathology.
- To examine ex vivo and in vivo evidence for iron accumulation in HD brains.
Main Methods:
- Literature review of existing hypotheses on HD pathology.
- Analysis of ex vivo studies examining iron levels in HD patient samples.
- Review of in vivo magnetic resonance imaging (MRI) findings in manifest and premanifest HD patients.
Main Results:
- Both ex vivo and in vivo studies support the presence of excess iron in the brains of HD patients.
- Evidence for iron accumulation as the primary initiator of HD pathology is limited, especially in early disease stages.
- Iron dysregulation contributes to oxidative stress and free radical toxicity in the context of HD.
Conclusions:
- Excess iron is a feature of the Huntington's disease brain.
- Iron accumulation is unlikely to be the initial trigger for HD pathogenesis.
- Further investigation is required to fully understand iron's contribution to HD progression and neurodegeneration.
Abstract:
Huntington's disease (HD) is a devastating neurological disorder that affects the brain. The cause of HD is an expanded CAG trinucleotide repeat in the Htt gene. The Htt gene is responsible for the protein huntingtin, the exact functions of which have yet to be elucidated. The role of iron in the pathological cascade is usually mentioned in the context of an inability to regulate iron homeostasis, which generates a surplus of reactive iron and free radical toxicity, resulting in increased oxidative stress. In this review, we discuss the role of iron within the existing hypotheses of HD pathology, ex vivo findings in support of increased iron in HD, and finally in vivo MRI findings in manifest and premanifest HD. Both in vivo and ex vivo findings support the notion that excess iron is present in the brain of HD patients. There does not seem to be much evidence that iron accumulation is the initiator of the pathological cascade as little or no evidence can be found for very early increased iron in the HD brain, when neuronal cell loss is already extensive.
