Related Experiment Video
Updated: Oct 15, 2025
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Metabolism in Huntington's disease: a major contributor to pathology
Akanksha Singh1, Namita Agrawal2
1Department of Zoology, University of Delhi, New Delhi, 110007, India.
Insights
Huntington's disease involves widespread metabolic changes affecting nearly every organ, often preceding neurological symptoms. These metabolic disruptions could serve as early biomarkers for disease onset and progression.
Area of Science:
- Neuroscience
- Genetics
- Metabolic Disorders
Background:
- Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by CAG repeat expansion in the Huntingtin gene, leading to mutant Huntingtin protein (mHTT).
- While neuronal death in cortico-striatal circuits is characteristic, HD also causes significant whole-body metabolic dysfunctions across multiple organs.
- These metabolic abnormalities, including weight fluctuation and glucose homeostasis issues, often appear years before hallmark neurological symptoms like chorea and cognitive decline.
Purpose of the Study:
- To provide a comprehensive review of central and peripheral metabolic abnormalities in Huntington's disease.
- To explore the potential of metabolic biomolecules as biomarkers for HD onset and progression.
- To discuss the efficacy of current therapies targeting metabolic remediation in HD.
Main Methods:
- Review of clinical and experimental studies on Huntington's disease.
- Analysis of metabolic alterations in energy, protein, nucleic acid, lipid, and carbohydrate metabolism.
- Evaluation of existing therapeutic strategies for metabolic dysfunction in HD.
Main Results:
- Significant central and peripheral metabolic abnormalities are integral to Huntington's disease pathology.
- Metabolic changes, such as altered body weight and glucose homeostasis, are recognized as reliable predictors of disease progression.
- Metabolic biomolecules show promise as early diagnostic and prognostic biomarkers for HD.
Conclusions:
- Metabolic abnormalities are a core feature of Huntington's disease, detectable before neurological symptoms.
- Metabolic biomarkers could significantly improve early diagnosis and monitoring of HD progression.
- Combination therapies targeting both neuronal protection and metabolic support may offer superior therapeutic outcomes compared to symptomatic treatments.
Abstract:
Huntington's disease (HD) is a progressively debilitating neurodegenerative disease exhibiting autosomal-dominant inheritance. It is caused by an unstable expansion in the CAG repeat tract of HD gene, which transforms the disease-specific Huntingtin protein (HTT) to a mutant form (mHTT). The profound neuronal death in cortico-striatal circuits led to its identification and characterisation as a neurodegenerative disease. However, equally disturbing are the concomitant whole-body manifestations affecting nearly every organ of the diseased individuals, at varying extents. Altered central and peripheral metabolism of energy, proteins, nucleic acids, lipids and carbohydrates encompass the gross pathology of the disease. Intense fluctuation of body weight, glucose homeostasis and organ-specific subcellular abnormalities are being increasingly recognised in HD. Many of these metabolic abnormalities exist years before the neuropathological manifestations such as chorea, cognitive decline and behavioural abnormalities develop, and prove to be reliable predictors of the disease progression. In this review, we provide a consolidated overview of the central and peripheral metabolic abnormalities associated with HD, as evidenced from clinical and experimental studies. Additionally, we have discussed the potential of metabolic biomolecules to translate into efficient biomarkers for the disease onset as well as progression. Finally, we provide a brief outlook on the efficacy of existing therapies targeting metabolic remediation. While it is clear that components of altered metabolic pathways can mark many aspects of the disease, it is only conceivable that combinatorial therapies aiming for neuronal protection in consort with metabolic upliftment will prove to be more efficient than the existing symptomatic treatment options.
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