Retinoic acid signaling in axonal regeneration
نویسندگان
چکیده
Following an acute central nervous system (CNS) injury, axonal regeneration and functional recovery are extremely limited. This is due to an extrinsic inhibitory growth environment and the lack of intrinsic growth competence. Retinoic acid (RA) signaling, essential in developmental dorsoventral patterning and specification of spinal motor neurons, has been shown through its receptor, the transcription factor RA receptor β2 (RARβ2), to induce axonal regeneration following spinal cord injury (SCI). Recently, it has been shown that in dorsal root ganglion neurons (DRGs), cAMP levels were greatly increased by lentiviral RARβ2 expression and contributed to neurite outgrowth. Moreover, RARβagonists, in cerebellar granule neurons (CGN) and in the brain in vivo, induced phosphoinositide 3-kinase dependent phosphorylation of AKT that was involved in RARβ-dependent neurite outgrowth. More recently, RA-RARβpathways were shown to directly transcriptionally repress a member of the inhibitory Nogo receptor (NgR) complex, Lingo-1, under an axonal growth inhibitory environment in vitro as well as following spinal injury in vivo. This perspective focuses on these newly discovered molecular mechanisms and future directions in the field.
منابع مشابه
Mechanisms of spinal cord injury regeneration in zebrafish: a systematic review
Objective(s):To determine the molecular and cellular mechanisms of spinal cord regeneration in zebrafish. Materials and Methods: Medical databases of PubMed and Scopus were searched with following key words: Zebrafish; spinal cord injuries; regeneration; recovery of function. The map of mechanisms was performed using Xmind software. Results: Wnt/ß-catenin signaling, L1.1, L1.2, Major vault prot...
متن کاملRetinoic acid synthesis by NG2 expressing cells promotes a permissive environment for axonal outgrowth
Stimulation of retinoic acid (RA) mediated signalling pathways following neural injury leads to regeneration in the adult nervous system and numerous studies have shown that the specific activation of the retinoic acid receptor β (RARβ) is required for this process. Here we identify a novel mechanism by which neuronal RARβ activation results in the endogenous synthesis of RA which is released i...
متن کاملRetinoic acid as a regulator of cytokine signaling after nerve injury.
After an injury of the central nervous system it is of foremost clinical concern to prevent nerve cell degeneration and to develop strategies for the support of axonal regeneration. This requires an understanding of traumatic processes in the nervous system and their regulation by intercellular cytokine signaling. Although injury-induced temporal changes in gene expression of many cytokines hav...
متن کاملAll-trans Retinoic Acid Regulates the Balance of Treg-Th17 Cells through ERK and P38 Signaling Pathway
متن کامل
Effects of retinoic acid in the mouse olfactory sensory systems
.................................................................................................. 5 SVENSK SAMMANFATTNING .............................................................. 6 PAPERS IN THIS THESIS .......................................................................... 7 ABBREVIATIONS ....................................................................................... 8 INTROD...
متن کامل