Acetylation and Wallerian degeneration
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1
University of Liege, GIGA - Neurosciences, Belgium
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2
University of Liege, GIGA - Unit of Signal Transduction, Belgium
Wallerian degeneration (WD) is the sequence of molecular and cellular events occurring to the degenerating distal portion of axons after injury. Whereas this process is fast and efficient in the peripheral nervous system (PNS), resulting in a favourable environment through which axons regrow towards their target, it is slow and incomplete in the central nervous system, leading to abortive axonal regeneration and failure of functional recovery. Thus, understanding the mechanisms that facilitate regeneration in the PNS is fundamental to develop effective therapies. Schwann cells (SCs) play a key role in the correct sequence of axon degeneration, regeneration and remyelination, by adopting successively de-differentiated and differentiated states. WD notably requires a precise regulation of transcriptional programs and post-transcritptional and post-translational modifications. Among these ones, acetylation can regulate diverse cellular processes such as proliferation, differentiation or metabolism by controlling protein activity, stability and localization. It has been recently shown that the Elp3 subunit of the Elongator complex, capable of acetylating proteins, is involved in several processes such as cell migration or differentiation and has been associated to different physiopathological contexts of the nervous system.
In order to assess the potential involvement of Elp3 within CSs during Wallerian degeneration and axon regeneration, we created a transgenic mouse in which the Elp3 subunit is specifically invalidated in SCs after tamoxifen treatment. A complete section of the sciatic nerve was performed to induce WD in these mice. Our preliminary results suggest that Elp3 is not required in SCs in physiological conditions but that its presence might be indispensable in stress conditions such as a peripheral nerve injury. Indeed, the absence of Elp3 in SCs seems to decrease axonal regeneration, muscle reinnervation and functional recovery compared to control mice. Moreover, in regenerated axons, the absence of Elp3 seems to improve remyelination, raising the hypothesis that Elp3 is favourable to a de-differentiated state of SCs. Therefore, these preliminary results suggest a role for Elp3 in the successive states of differentiation/de-differentiation of SCs during axonal degeneration, regeneration and remyelination.
Keywords:
Acetylation,
Schwann Cells,
Wallerian Degeneration,
axonal regeneration,
Remyellination
Conference:
Belgian Brain Council, Liège, Belgium, 27 Oct - 27 Oct, 2012.
Presentation Type:
Poster Presentation
Topic:
Other basic/clinical neurosciences topic
Citation:
Boerboom
A,
Chaballe
L,
Close
P,
Schoenen
J,
Chariot
A and
Franzen
R
(2012). Acetylation and Wallerian degeneration.
Conference Abstract:
Belgian Brain Council.
doi: 10.3389/conf.fnhum.2012.210.00079
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Received:
03 Sep 2012;
Published Online:
12 Sep 2012.
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Correspondence:
Miss. Angélique Boerboom, University of Liege, GIGA - Neurosciences, Liège, 4000, Belgium, aboerboom@student.ulg.ac.be