Beta secretase activity in peripheral nerve regeneration

Carolyn Tallon, Mohamed H. Farah

Research output: Contribution to journalReview articlepeer-review

Abstract

While the peripheral nervous system has the capacity to regenerate following a nerve injury, it is often at a slow rate and results in unsatisfactory recovery, leaving patients with reduced function. Many regeneration associated genes have been identified over the years, which may shed some insight into how we can manipulate this intrinsic regenerative ability to enhance repair following peripheral nerve injuries. Our lab has identified the membrane bound protease beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), or beta secretase, as a potential negative regulator of peripheral nerve regeneration. When beta secretase activity levels are abolished via a null mutation in mice, peripheral regeneration is enhanced following a sciatic nerve crush injury. Conversely, when activity levels are greatly increased by overexpressing beta secretase in mice, nerve regeneration and functional recovery are impaired after a sciatic nerve crush injury. In addition to our work, many substrates of beta secretase have been found to be involved in regulating neurite outgrowth and some have even been identified as regeneration associated genes. In this review, we set out to discuss BACE1 and its substrates with respect to axonal regeneration and speculate on the possibility of utilizing BACE1 inhibitors to enhance regeneration following acute nerve injury and potential uses in peripheral neuropathies.

Original languageEnglish (US)
Pages (from-to)1565-1574
Number of pages10
JournalNeural Regeneration Research
Volume12
Issue number10
DOIs
StatePublished - Oct 2017

Keywords

  • Axonal regeneration
  • Beta-site amyloid precursor protein-cleaving enzyme 1
  • Peripheral nerve

ASJC Scopus subject areas

  • Developmental Neuroscience

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