Diltiazem Promotes Regenerative Axon Growth

  • Mol Neurobiol. 2019 Jun;56(6):3948-3957. doi: 10.1007/s12035-018-1349-5.
Eric A Huebner  1  2 ,  Stéphane Budel  2 ,  Zhaoxin Jiang  2 ,  Takao Omura  1 ,  Tammy Szu-Yu Ho  1 ,  Lee Barrett  1 ,  Janie S Merkel  3 ,  Luis M Pereira  4 ,  Nick A Andrews  1 ,  Xingxing Wang  2 ,  Bhagat Singh  1 ,  Kush Kapur  1 ,  Michael Costigan  1  4 ,  Stephen M Strittmatter  5 ,  Clifford J Woolf  6
Affiliations
  • 1. F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
  • 2. Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT, 06520, USA.
  • 3. Yale Center for Molecular Discovery, Yale University, West Haven, CT, 06516, USA.
  • 4. Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
  • 5. Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT, 06520, USA. [email protected].
  • 6. F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. [email protected].
PMID: 30232777 DOI: 10.1007/s12035-018-1349-5
Abstract

Axotomy results in permanent loss of function after brain and spinal cord injuries due to the minimal regenerative propensity of the adult central nervous system (CNS). To identify pharmacological enhancers of axon regeneration, 960 compounds were screened for cortical neuron axonal regrowth using an in vitro cortical scrape assay. Diltiazem, verapamil, and bromopride were discovered to facilitate axon regeneration in rat cortical cultures, in the presence of chondroitin sulfate proteoglycans (CSPGs). Diltiazem, an L-type calcium channel blocker (L-CCB), also promotes axon outgrowth in adult primary mouse dorsal root ganglion (DRG) and induced human sensory (iSensory) neurons.

Keywords
Axon regeneration; Chondroitin sulfate proteoglycans; Cortical neurons; Diltiazem; Scrape assay; Sensory neurons.
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