Faculty Collaboration Database

Selecting optimal combinations of transcription factors to promote axon regeneration: Why mechanisms matter. Neurosci Lett 2017 Jun 23;652:64-73

Date

12/28/2016

Pubmed ID

28025113

Pubmed Central ID

PMC5466899

DOI

10.1016/j.neulet.2016.12.032

Scopus ID

2-s2.0-85009507974 (requires institutional sign-in at Scopus site)   27 Citations

Abstract

Recovery from injuries to the central nervous system, including spinal cord injury, is constrained in part by the intrinsically low ability of many CNS neurons to mount an effective regenerative growth response. To improve outcomes, it is essential to understand and ultimately reverse these neuron-intrinsic constraints. Genetic manipulation of key transcription factors (TFs), which act to orchestrate production of multiple regeneration-associated genes, has emerged as a promising strategy. It is likely that no single TF will be sufficient to fully restore neuron-intrinsic growth potential, and that multiple, functionally interacting factors will be needed. An extensive literature, mostly from non-neural cell types, has identified potential mechanisms by which TFs can functionally synergize. Here we examine four potential mechanisms of TF/TF interaction; physical interaction, transcriptional cross-regulation, signaling-based cross regulation, and co-occupancy of regulatory DNA. For each mechanism, we consider how existing knowledge can be used to guide the discovery and effective use of TF combinations in the context of regenerative neuroscience. This mechanistic insight into TF interactions is needed to accelerate the design of effective TF-based interventions to relieve neuron-intrinsic constraints to regeneration and to foster recovery from CNS injury.

Author List

Venkatesh I, Blackmore MG

Author

Murray Blackmore PhD Assistant Professor in the School of Allied Health department at Marquette University

MESH terms used to index this publication - Major topics in bold

Animals
Axons
Brain
Genetic Loci
Humans
Nerve Regeneration
Peripheral Nerves
Spinal Cord
Spinal Cord Injuries
Transcription Factors