Biology Reference
In-Depth Information
Detection of nuclear p-STAT3 correlates with upregulated transcription of
STAT3-responsive genes. Functionally, axonal STAT3 and its retrograde
transport to the cell body prevent sensory neuronal death after
axotomy but exert minimal effect on axon growth ( Ben-Yaakov et al.,
2012 ). It was also suggested that delay in detection of nuclear p-STAT3
depends on distance between the injury site and cell body ( Ben-Yaakov
et al., 2012 ). Overall, these findings indicate that STAT3 could have diverse
roles, from conveying injury signals to the cell body, to facilitating gene
transcription and mitochondrial function in order to foster axon regeneration.
However, the detailed mechanisms underlying STAT3's effects on axon
growth remain to be elucidated.
4. SYNERGISTIC EFFECTS FROM SIMULTANEOUSLY
TARGETING PTEN AND OTHER GROWTH-PROMOTING
FACTORS
The process of axon regeneration is multifaceted that requires activa-
tion of the regenerative program in response to injury signals to initiate
growth cone formation, followed by sustained axon extension. This process
is likely mediated by activation and modification of multiple signaling path-
ways working in concert, leading to enhanced gene transcription and pro-
tein translation. In the visual system, deletion of either PTEN or SOCS3
alone in adult RGCs promotes some degree of axon regeneration ( Park
et al., 2008; Smith et al., 2009 ), but the regeneration occurs shortly after
injury, subsides substantially, and involves only a small population of total
retinal neurons after single treatments. However, combining PTEN
deletion with other growth-enhancing factors results in much more
robust axon regeneration when compared to targeting PTEN alone. For
instance, intraocular inflammation is known to stimulate RGC axon
regeneration after lesion ( Fischer, Heiduschka, & Thanos, 2001; Leon,
Yin, Nguyen, Irwin, & Benowitz, 2000 ). cAMP elevation has a minimal
effect on its own but enhances CNTF ( Cui, Yip, Zhao, So, & Harvey,
2003 ) or inflammation effects on axon growth ( Yin et al., 2006, 2009 ).
PTEN deletion in RGCs combined with inflammation and cAMP
analogues promotes a much greater extent of axon regeneration in the
optic nerve compared to targeting them individually ( Kurimoto et al.,
2010 ). More recently, double deletion of PTEN and SOCS3 was shown
to result in much stronger CNS axon regeneration compared to deleting
either gene alone ( Sun et al., 2011 ).
Search WWH ::




Custom Search