Neuroimmunophilins: Novel neuroprotective and neuroregenerative targets

Authors

  • Xin Guo PhD,

    1. Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD
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  • James F. Dillman III PhD,

    1. Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD
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  • Valina L. Dawson PhD,

    Corresponding author
    1. Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD
    2. Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD
    3. Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD
    • Departments of Neurology and Neuroscience, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Carnegie 214, Baltimore, MD 21287
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  • Ted M. Dawson MD, PhD

    1. Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD
    2. Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD
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Abstract

Cyclosporin A (CsA) and FK506 (tacrolimus) are immunosuppresants that are widely used in organ transplantation. CsA is an 11-member cyclic peptide, whereas FK506 is a macrolide antibiotic. Recently, these powerful and useful compounds have become of great interest to neuroscientists for their unique neuroprotective and neuroregenerative effects. These drugs and nonimmunosuppressive analogs protect neurons from the effects of glutamate excitotoxicity, focal ischemia, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic cell death. They also stimulate functional recovery of neurons in a variety of neurologic injury paradigms. These drugs exert their effects via immunophilins, the protein receptors for these agents. The immunophilin ligands show particular promise as a novel class of neuroprotective and neuroregenerative agents that have the potential to treat a variety of neurologic disorders.

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