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Preclinical and clinical otoprotective applications of cell-penetrating peptide D-JNKI-1 (AM-111).

Abstract
There is a growing interest in the auditory community to develop novel prophylactic and therapeutic drugs to prevent permanent sensorineural hearing loss following acute cochlear injury. The jun-N-terminal protein kinase (JNK) pathway plays a crucial role in acute sensory hearing loss. Blocking the JNK pathway using the cell-penetrating peptide D-JNKI-1 (AM-111/brimapitide) has shown promise as both a prophylactic and therapeutic agent for acute cochlear injury. A number of pre-clinical and clinical studies have determined the impact of D-JNKI-1 on acute sensorineural hearing loss. Given the inner-ear selective therapeutic profile, local route of administration, and ability to diffuse across cellular membranes rapidly using both active and passive transport makes D-JNK-1 a promising oto-protective drug. In this review article, we discuss the application of D-JNKI-1 in various auditory disorders as well as its pharmacological properties and distribution in the cochlea.
AuthorsAdrien A Eshraghi, Mayank Aranke, Richard Salvi, Dalian Ding, John K M Coleman Jr, Emre Ocak, Rahul Mittal, Thomas Meyer
JournalHearing research (Hear Res) Vol. 368 Pg. 86-91 (10 2018) ISSN: 1878-5891 [Electronic] Netherlands
PMID29573879 (Publication Type: Journal Article, Review)
CopyrightCopyright © 2018 Elsevier B.V. All rights reserved.
Chemical References
  • Cell-Penetrating Peptides
  • Enzyme Inhibitors
  • Peptides
  • JNK Mitogen-Activated Protein Kinases
  • D-JNKI-1
Topics
  • Animals
  • Cell Membrane Permeability
  • Cell-Penetrating Peptides (administration & dosage)
  • Cochlea (drug effects, enzymology, injuries, physiopathology)
  • Cochlear Diseases (complications, drug therapy, enzymology, physiopathology)
  • Cytoprotection
  • Enzyme Inhibitors (administration & dosage)
  • Hearing (drug effects)
  • Hearing Loss, Sensorineural (enzymology, etiology, physiopathology, prevention & control)
  • Humans
  • JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
  • Peptides (administration & dosage)
  • Prognosis
  • Risk Factors
  • Signal Transduction (drug effects)

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