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Metabolic Dysregulation in Amyotrophic Lateral Sclerosis: Challenges and Opportunities

  • Neurogenetics and Psychiatric Genetics (M Hiltunen and DR Marenda, Section Editors)
  • Published:
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Abstract

Purpose of Review

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease for which there is no cure and treatments are at best palliative. Several genes have been linked to ALS, which highlight defects in multiple cellular processes including RNA processing, proteostasis, and metabolism. Clinical observations have identified glucose intolerance and dyslipidemia as key features of ALS; however, the causes of these metabolic alterations remain elusive.

Recent Findings

Recent studies reveal that motor neurons and muscle cells may undergo cell type-specific metabolic changes that lead to utilization of alternate fuels. For example, ALS patients’ muscles exhibit reduced glycolysis and increased reliance on fatty acids. In contrast, ALS motor neurons contain damaged mitochondria and exhibit impaired lipid beta oxidation, potentially leading to increased glycolysis as a compensatory mechanism.

Summary

These findings highlight the complexities of metabolic alterations in ALS and provide new opportunities for designing therapeutic strategies based on restoring cellular energetics.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA

    Archi Joardar, Ernesto Manzo & Daniela C. Zarnescu

  2. Department of Neuroscience, University of Arizona, Tucson, AZ, 85721, USA

    Daniela C. Zarnescu

  3. Department of Neurology, University of Arizona, Tucson, AZ, 85721, USA

    Daniela C. Zarnescu

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  1. Archi Joardar
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  2. Ernesto Manzo
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Correspondence to Daniela C. Zarnescu.

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Archi Joardar and Ernesto Manzo declare that they have no conflict of interest.

Daniela C. Zarnescu has a patent pending.

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This article is part of the Topical Collection on Neurogenetics and Psychiatric Genetics

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Joardar, A., Manzo, E. & Zarnescu, D.C. Metabolic Dysregulation in Amyotrophic Lateral Sclerosis: Challenges and Opportunities. Curr Genet Med Rep 5, 108–114 (2017). https://doi.org/10.1007/s40142-017-0123-8

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