Enhancing adult nerve regeneration through the knockdown of retinoblastoma protein

Kimberly J. Christie, Anand Krishnan, Jose A. Martinez, Kaylynn Purdy, Bhagat Singh, Shane Eaton and Douglas Zochodne ()
Additional contact information
Kimberly J. Christie: University of Calgary
Anand Krishnan: University of Calgary
Jose A. Martinez: University of Calgary
Kaylynn Purdy: University of Calgary
Bhagat Singh: University of Calgary
Shane Eaton: University of Calgary
Douglas Zochodne: University of Calgary

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract Tumour suppressor pathways may offer novel targets capable of altering the plasticity of post-mitotic adult neurons. Here we describe a role for the retinoblastoma (Rb) protein, widely expressed in adult sensory neurons and their axons, during regeneration. In adult sensory neurons, Rb short interfering RNA (siRNA) knockdown or Rb1 deletion in vitro enhances neurite outgrowth and branching. Plasticity is achieved in part through upregulation of neuronal PPARυ; its antagonism inhibits Rb siRNA plasticity, whereas a PPARυ agonist increases growth. In an in vivo regenerative paradigm following complete peripheral nerve trunk transection, direct delivery of Rb siRNA prompts increased outgrowth of axons from proximal stumps and entrains Schwann cells to accompany them for greater distances. Similarly, Rb siRNA delivery following a nerve crush improves behavioural indices of motor and sensory recovery in mice. The overall findings indicate that inhibition of tumour suppressor molecules has a role to play in promoting adult neuron regeneration.

Date: 2014
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms4670 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4670

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms4670

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().