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EAAT2 and the Molecular Signature of Amyotrophic Lateral Sclerosis

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Glial Amino Acid Transporters

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 16))

Abstract

Amyotrophic lateral sclerosis (ALS) is a rapid and fatal neurodegenerative disease, primarily affecting upper and lower motor neurons. It is an extremely heterogeneous disease in both cause and symptom development, and its mechanisms of pathogenesis remain largely unknown. Excitotoxicity, a process caused by excessive glutamate signaling, is believed to play a substantial role, however. Excessive glutamate release, changes in postsynaptic glutamate receptors, and reduction of functional astrocytic glutamate transporters contribute to excitotoxicity in ALS. Here, we explore the roles of each, with a particular emphasis on glutamate transporters and attempts to increase them as therapy for ALS. Screening strategies have been employed to find compounds that increase the functional excitatory amino acid transporter EAAT2 (GLT1), which is responsible for the vast majority of glutamate clearance. One such compound, ceftriaxone, was recently tested in clinical trials but unfortunately did not modify disease course, though its effect on EAAT2 expression in patients was not measured.

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Authors and Affiliations

  1. Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University, 900 Walnut St, Philadelphia, PA, 19107, USA

    Lauren Taylor Rosenblum & Davide Trotti

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  1. Lauren Taylor Rosenblum
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  2. Davide Trotti
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Correspondence to Lauren Taylor Rosenblum .

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Editors and Affiliations

  1. Department of Toxicology, Cinvestav-IPN México City, México, Mexico

    Arturo Ortega

  2. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Arne Schousboe

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Rosenblum, L.T., Trotti, D. (2017). EAAT2 and the Molecular Signature of Amyotrophic Lateral Sclerosis. In: Ortega, A., Schousboe, A. (eds) Glial Amino Acid Transporters. Advances in Neurobiology, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-319-55769-4_6

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