Impaired Redox Signaling in Huntington's Disease: Therapeutic Implications

Huntington's disease (HD) is a neurodegenerative disease triggered by expansion of polyglutamine repeats in the protein huntingtin. Mutant huntingtin (mHtt) aggregates and elicits toxicity by multiple mechanisms which range from dysregulated transcription to disturbances in several metabolic pa...

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Bibliographic Details
Published in:Frontiers in molecular neuroscience 2019-03, Vol.12, p.68
Main Authors: Paul, Bindu D, Snyder, Solomon H
Format: Article
Language:English
Subjects:
Antioxidants
Autophagy
Bioenergetics
Cancer
cysteine
Defense mechanisms
Deoxyribonucleic acid
Disease
DNA
DNA damage
Enzymes
Free radicals
Homeostasis
Huntingtin
Huntington's disease
Iron
Lipid peroxidation
Lipids
Metabolic pathways
Metals
Mitochondria
Neurodegeneration
Neurodegenerative diseases
Neuroscience
Oxidation
Oxidative stress
Pathophysiology
Polyglutamine
redox signaling
Therapeutic applications
Toxicity
Transcription
Trinucleotide repeat diseases
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Summary:Huntington's disease (HD) is a neurodegenerative disease triggered by expansion of polyglutamine repeats in the protein huntingtin. Mutant huntingtin (mHtt) aggregates and elicits toxicity by multiple mechanisms which range from dysregulated transcription to disturbances in several metabolic pathways in both the brain and peripheral tissues. Hallmarks of HD include elevated oxidative stress and imbalanced redox signaling. Disruption of antioxidant defense mechanisms, involving antioxidant molecules and enzymes involved in scavenging or reversing oxidative damage, have been linked to the pathophysiology of HD. In addition, mitochondrial function is compromised in HD leading to impaired bioenergetics and elevated production of free radicals in cells. However, the exact mechanisms linking redox imbalance to neurodegeneration are still elusive. This review will focus on the current understanding of aberrant redox homeostasis in HD and potential therapeutic interventions.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2019.00068