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Branched Chain Amino Acids in Experimental Models of Amyotrophic Lateral Sclerosis

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Branched Chain Amino Acids in Clinical Nutrition

Part of the book series: Nutrition and Health ((NH))

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Abstract

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease whose etiology is still obscure. The most common mutations found in familiar ALS are localized in the gene codifying the copper-zinc superoxide dismutase 1 (SOD1) enzyme which, however, explains only about 20% of familiar ALS and 2% of the sporadic form of this disease.

The vast majority of patients is affected by the sporadic form of the disease and a possible role of environmental factors interacting with several defective genes may be suggested. In particular, several epidemiological studies have shown a higher risk of ALS among Italian and American soccer players; among the possible risk factors, the excessive use of dietary integrators, specifically the branched-chain amino acids (BCAAs) valine, isoleucine and leucine has attracted some interest.

The hypothesis of potential neurotoxic effects of BCAAs on brain functions is supported by the evidences that BCAAs enter the brain through a transporter located at the blood-brain barrier, where they contribute to de novo synthesis of glutamate, the principal excitatory neurotransmitter of the central nervous system.

In this chapter we will briefly present four studies investigating the potential neurotoxicity of BCAAs and their possible implication in neurodegenerative diseases with either in vitro or in vivo models.

Our in vitro results suggest that BCAAs are neurotoxic in both neuronal and astrocytic cultures through the overstimulation of glutamate pathways: BCAAs alter the expression of genes linked to oxidative stress and to immune properties of microglial cells, possibly favoring the onset of neurodegeneration. Furthermore, our in vivo findings confirmed that chronic dietary intake of BCAAs worsens the motor coordination deficit of the G93A-SOD1 mice, a transgenic model of ALS. In addition, the electrophysiological results indicated that the BCAA diet restored the glutamate neurotransmission, normally altered in this strain of mutated mice.

Overall, our experimental evidences provide a possible link between an environmental factor (high intake of BCAAs) and the increased risk of neurotoxic/neurodegenerative damage in individuals with a specific genetic predisposition.

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Author information

Authors and Affiliations

  1. Unit of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy

    Alessia De Felice Master Degree in Biology & Gemma Calamandrei Master Degree in Biology

  2. Section of Clinic, Diagnostic and Therapy of Degenerative Diseases of the Central Nervous System, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy

    Annamaria Confaloni Ph.D. & Alessio Crestini Ph.D., M.S., M.Sc. Res. Master of Science, Post-graduate in applied genetics and molecular biology, M.Sc.Res, Master Degree in Biology

  3. Section of Experimental Neurology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy

    Roberta De Simone M.Sc. & Luisa Minghetti Ph.D.

  4. Section of Molecular Neurobiology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy

    Fiorella Malchiodi-Albedi M.D. & Andrea Matteucci Ph.D., Biology

  5. Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy

    Alberto Martire Ph.D. & Patrizia Popoli M.D.

  6. Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy

    Aldina Venerosi Ph.D.

Authors
  1. Alessia De Felice Master Degree in Biology
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  2. Annamaria Confaloni Ph.D.
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  3. Alessio Crestini Ph.D., M.S., M.Sc. Res. Master of Science, Post-graduate in applied genetics and molecular biology, M.Sc.Res, Master Degree in Biology
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  4. Roberta De Simone M.Sc.
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  5. Fiorella Malchiodi-Albedi M.D.
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  6. Alberto Martire Ph.D.
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  7. Andrea Matteucci Ph.D., Biology
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  8. Luisa Minghetti Ph.D.
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  9. Patrizia Popoli M.D.
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  10. Aldina Venerosi Ph.D.
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  11. Gemma Calamandrei Master Degree in Biology
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Corresponding author

Correspondence to Gemma Calamandrei Master Degree in Biology .

Editor information

Editors and Affiliations

  1. Intensive Care, Barnet and Chase Farm Hospitals, Royal Free London NHS Foundation Trust, London, United Kingdom

    Rajkumar Rajendram

  2. Diabetes and Nutritional Sciences, Kings College London, London, United Kingdom

    Victor R. Preedy

  3. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

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De Felice, A. et al. (2015). Branched Chain Amino Acids in Experimental Models of Amyotrophic Lateral Sclerosis. In: Rajendram, R., Preedy, V., Patel, V. (eds) Branched Chain Amino Acids in Clinical Nutrition. Nutrition and Health. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1923-9_19

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  • DOI: https://doi.org/10.1007/978-1-4939-1923-9_19

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  • Publisher Name: Humana Press, New York, NY

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