Abstracts (poster) - Wissenschaft Online

Perrine Gaub, Andrea Tedeschi, Antonio Schmandke, Radhika Puttagunta, Tuan
Nguyen, Simone Di Giovanni
Enhancement of neuronal acetylation promotes neurite and
axon outgrowth
Spontaneous axon regeneration following injury in the central nervous system is
extremely limited due to the presence of an inhibitory environment, mediated by
disrupted myelin and extracellular matrix proteins, and to a deficiency of the intrinsic proaxon
outgrowth gene expression program.
Here, we have employed a novel strategy to switch the intrinsic neuronal genetic
program from a “non permissive” to a “permissive” pattern for neurite/axon outgrowth
by increasing acetylation by facilitating the histone acetyltransferases (HAT) activity. In
fact, HAT regulate the remodelling of chromatin and of the dynamic changes in the
nucleosomal packaging, by transferring acetyl groups to core histone proteins and
transcription factors. These modifications promote chromatin relaxation, accessibility to
chromosomal DNA, and ultimately facilitate transcription.
Previously, increased neuronal acetylation has been shown to protect from apoptosis and
to promote differentiation..
Here, we show that the enhancement of endogenous acetylation in neurons, by using
specific deacetylase inhibitory drugs, leads to increased neurite/axon outgrowth.
Specifically, we demonstrate that increased acetylation enhances axon outgrowth and
reduced growth cone collapse in primary neurons on both permissive (poly-D-lysine) and
non-permissive (myelin, CSPG) substrates. In addition, we show that these effects are
largely dependent upon the HATs CBP/p300 and P/CAF and the acetylation of the
transcription factor p53.
Finally, in vivo experiments in models of axon injury further address the relevance of
acetylation on axon regeneration.
These findings may contribute to developing new strategies for axonal outgrowth and
regeneration after injury.
contact:
MD, PhD Simone Di Giovanni
University of Tuebingen
HIH
simone.digiovanni@medizin.uni-tuebingen.de
otfried mueller strasse 27
72076 Tuebingen (Germany)