Novel targets to improve axonal regeneration in the CNS: the role of myelin lipid inhibitors, injury signals and axonal transport (original) (raw)
Activating transcription factor 3 ATP Adenosine-5'-triphosphate BBB Blood-brain-barrier BDNF Brain-derived neurotrophic factor C3 C3-ADP-ribosyltransferase cAMP Cyclic adenosine monophosphate CE Cholesteryl esters Cer Ceramide cGMP Cyclic guanosine monophosphate CGN Cerebellar granule neurons CNS Central nervous system CO Cholesterol CREB cAMP response element-binding protein CRMP-2 Collapsin response mediator protein 2 Csk C-terminal Src kinase CSPG Chondroitin sulfate proteoglycans Abbreviation list 18 CST Corticospinal tract CTB Cholera toxin B clubs of the axons interrupted inside the white matter (central stumps). Two main varieties are presented: a. From a thick, terminal (retraction ball) or en passant varicosity arise several fine and pale radiations that get lost in the neighboring territories where they ramify and end in a pale tip. Because it evokes the shape of the tortoise, I named such a singular disposition the testudinoid apparatus. Although many advances have been made in the axonal regeneration field, and despite that several molecular mechanisms underlying axonal growth have been dissected, the general view has not changed greatly since the first descriptions by Ramon y Cajal. To date, despite of the several ongoing clinical trials, still only very limited axonal regeneration is achieved in the CNS. As such, new studies to understand and improve regeneration of CNS axons are of the utmost importance. along the radial glial process and leaves behind a trailing process that elongates tangentially in the intermediate zone (purple, 5). The cell body continues to migrate towards its final destination (the top of the cortical plate), while the axon rapidly elongates (6). The leading process gives rise to the apical dendrite (green, 7), which initiates local branching in the marginal zone (until radial A B blocks of the regrowing axons is obtained by local protein synthesis (Verma et al., 2005; Willis and Twiss, 2006; Gumy et al., 2010). Axonal mRNAs face great challenges: they need to be actively transported, stored and protected from degradation at their final destination. The RNA-binding proteins play an essential role in this process, by binding to cis-elements in the 5'-or 3'-untranslated regions (UTR). Upon RNA binding they control its transport, stability and translation (Bassell and Kelic, 2004; Patel et al., 2012). The best