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β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression

Author

Listed:
  • Jeffrey D. Rothstein

    (Department of Neurology
    Johns Hopkins University)

  • Sarjubhai Patel

    (Department of Neurology)

  • Melissa R. Regan

    (Department of Neurology)

  • Christine Haenggeli

    (Department of Neurology)

  • Yanhua H. Huang

    (Johns Hopkins University)

  • Dwight E. Bergles

    (Johns Hopkins University)

  • Lin Jin

    (Department of Neurology)

  • Margaret Dykes Hoberg

    (Department of Neurology)

  • Svetlana Vidensky

    (Department of Neurology)

  • Dorothy S. Chung

    (Department of Neurology)

  • Shuy Vang Toan

    (Department of Neurology)

  • Lucie I. Bruijn

    (The ALS Association)

  • Zao-zhong Su

    (Columbia University Medical Center, College of Physicians and Surgeons)

  • Pankaj Gupta

    (Columbia University Medical Center, College of Physicians and Surgeons)

  • Paul B. Fisher

    (Columbia University Medical Center, College of Physicians and Surgeons)

Abstract

Rewrite the pharmacopoeia The β-lactam antibiotics — penicillin and its semisynthetic derivatives — act by inhibiting bacterial synthetic pathways, and their success has in part been because they have little effect on their hosts. So it's a complete surprise to find that many of these β-lactams also act on the dominant excitatory neurotransmitter transporter system in the mammalian central nervous system. The mechanism of action involves activation of GLT1, the gene for glutamate transport. In animal models of ischaemic injury and motor neuron degeneration, ceftriaxone is neuroprotective, and in the animal model of the fatal disease amyotrophic lateral sclerosis (Lou Gehrig's disease), it increases the survival rate of mice. These studies provide a completely new drug target for scores of highly safe pharmaceuticals and may lead to new therapies for neurological disease.

Suggested Citation

  • Jeffrey D. Rothstein & Sarjubhai Patel & Melissa R. Regan & Christine Haenggeli & Yanhua H. Huang & Dwight E. Bergles & Lin Jin & Margaret Dykes Hoberg & Svetlana Vidensky & Dorothy S. Chung & Shuy Va, 2005. "β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression," Nature, Nature, vol. 433(7021), pages 73-77, January.
    • Handle: RePEc:nat:nature:v:433:y:2005:i:7021:d:10.1038_nature03180
    DOI: 10.1038/nature03180
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    Cited by:

    1. Xianhui Ruan & Wei Yan & Minghui Cao & Ray Anthony M. Daza & Miranda Y. Fong & Kaifu Yang & Jun Wu & Xuxiang Liu & Melanie Palomares & Xiwei Wu & Arthur Li & Yuan Chen & Rahul Jandial & Nicholas C. Sp, 2024. "Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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