The ability to stimulate functional neuronal regeneration would markedly enhance treatment of brain injuries and neurodegenerative diseases. In studies of C. elegans, Pinan-Lucarre et al. uncovered unexpected roles for apoptotic proteins in promoting neuronal regeneration that might be conserved across species. Worms mutant for CED-3, the core executioner apoptotic protease in C. elegans, had slower axonal outgrowth and delayed neuronal reconnections after laser-mediated injury. The CED-3-activating protein CED-4 [homologue of mammalian apoptosis protease activating factor-1 (Apaf-1)], but not other upstream apoptotic proteins, was also important. They also linked CED-3 and CED-4 to a pathway involving DLK-1, a kinase implicated in regeneration across species. Finally, they showed that this regenerative pathway involves Ca2+ signalling (known to be important in neuronal responses to injury) and specifically the conserved Ca2+-binding protein calreticulin. The authors propose a model whereby injury-induced Ca2+ signalling amplified by calreticulin promotes CED-4-mediated activation of CED-3, which then acts upstream of a DLK-1-mediated regenerative pathway. These data uncover a previously unknown pathway that will guide future studies of neuronal regeneration in higher organisms.
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RESEARCH HIGHLIGHT| 01 July 2012
Neuronal regeneration: a role for apoptotic proteins
Online Issn: 1754-8411
Print Issn: 1754-8403
Written by editorial staff. © 2012. Published by The Company of Biologists Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms
Dis Model Mech (2012) 5 (4): 415.
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Neuronal regeneration: a role for apoptotic proteins. Dis Model Mech 1 July 2012; 5 (4): 415. doi:
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