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Metabolic Alterations Amalgamated with Huntington’s Disease

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Book cover Insights into Human Neurodegeneration: Lessons Learnt from Drosophila

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Abstract

Huntington’s disease (HD) is a progressive monogenic neurodegenerative disease typified by loss of motor, psychiatric and cognitive function with no known cure. Additionally, the concomitant occurrence of metabolic disturbances including unintended weight loss has also been reported in HD patients. However, the pathophysiology remains largely unclear. The underlying pathophysiology comes further complex due to the ubiquitous expression of the causative huntingtin (HTT) gene. Research studies indicate functional changes in the peripheral organs of patients reflecting the involvement of peripheral component in metabolic disturbances observed in HD. Links between metabolic phenotype and neurodegeneration have also been suggested in HD patients. Altogether, these observations underscore the complexity of metabolic disturbances occurring in HD and accentuate the need to study this phenomenon in a combinatorial setting. Development of therapeutics targeting metabolic alterations in HD might abrogate some of the comorbidities and can substantially improve the quality of a patient’s life, and might even prevent premature death.

The fruit fly, Drosophila melanogaster, can provide a treasured genetic system to express the human huntingtin gene in a temporally regulated and tissue-specific pattern. Drosophila can contribute to deeper mechanistic insights into the metabolic defects underlying HD due to the presence of multiple evolutionarily conserved metabolic pathways. In this chapter, we highlight the genetics, epidemiology, and metabolic disturbances manifested in HD and how Drosophila melanogaster can be used as a powerful genetic model for unraveling the metabolic processes and pathways that go awry in HD as a foundation for translational research and developing new therapeutics.

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  1. Department of Zoology, University of Delhi, Delhi, India

    Priya Lakra & Namita Agrawal

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  1. Priya Lakra
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  2. Namita Agrawal
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  1. Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Mousumi Mutsuddi

  2. Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Ashim Mukherjee

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Lakra, P., Agrawal, N. (2019). Metabolic Alterations Amalgamated with Huntington’s Disease. In: Mutsuddi, M., Mukherjee, A. (eds) Insights into Human Neurodegeneration: Lessons Learnt from Drosophila. Springer, Singapore. https://doi.org/10.1007/978-981-13-2218-1_6

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