Hyperactivated Stat3 boosts axon regeneration in the CNS.
Hyperactivated Stat3 boosts axon regeneration in the CNS.
Exp Neurol. 2016 Apr 6;
Authors: Mehta ST, Luo X, Park KK, Bixby JL, Lemmon VP
Abstract
Axonal regeneration after spinal cord injury (SCI) is intrinsically and extrinsically inhibited by multiple factors. One major factor contributing to intrinsic regeneration failure is the inability of mature neurons in the central nervous system (CNS) to activate regeneration-associated transcription factors (TFs) post-injury. A prior study identified TFs overexpressed in neurons of the peripheral nervous system (PNS) compared to the CNS; some of these could be involved in the ability of PNS neurons to regenerate. Of these, signal transducer and activator of transcription 3 (STAT3), as well its downstream regeneration-associated targets, showed a significant upregulation in PNS neurons relative to CNS neurons, and a constitutively active variant of Stat3 (Stat3CA) promoted neurite growth when expressed in cerebellar neurons (Lerch etal., 2012; Smith etal., 2011). To further enhance STAT3's neurite outgrowth enhancing activity, Stat3CA was fused with a viral activation domain (VP16). VP16 hyperactivates TFs by recruiting transcriptional co-factors to the DNA binding domain (Hirai etal., 2010). Overexpression of this VP16-Stat3CA chimera in primary cortical neurons led to a significant increase of neurite outgrowth as well as Stat3 transcriptional activity invitro. Furthermore, invivo transdu...
Source: Experimental Neurology - Category: Neurology Authors: Mehta ST, Luo X, Park KK, Bixby JL, Lemmon VP Tags: Exp Neurol Source Type: research