PMID- 25009261 OWN - NLM STAT- MEDLINE DCOM- 20140909 LR - 20220408 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 34 IP - 28 DP - 2014 Jul 9 TI - Soluble adenylyl cyclase is necessary and sufficient to overcome the block of axonal growth by myelin-associated factors. PG - 9281-9 LID - 10.1523/JNEUROSCI.1434-14.2014 [doi] AB - Neurons in the CNS do not regenerate following injury; regeneration is blocked by inhibitory proteins in myelin, such as myelin-associated glycoprotein (MAG). Elevating neuronal levels of the second messenger cAMP overcomes this blocked axonal outgrowth. One way to elevate cAMP is pretreating neurons with neurotrophins, such as brain-derived neurotrophic factor (BDNF). However, pleiotropic effects and poor bioavailability make exogenous administration of neurotrophins in vivo problematic; therefore, alternative targets must be considered. In neurons, two families of adenylyl cyclases synthesize cAMP, transmembrane adenylyl cyclases (tmACs), and soluble adenylyl cyclase (sAC). Here, we demonstrate that sAC is the essential source of cAMP for BDNF to overcome MAG-dependent inhibition of neurite outgrowth. Elevating sAC in rat and mouse neurons is sufficient to induce neurite outgrowth on myelin in vitro and promotes regeneration in vivo. These results suggest that stimulators of sAC might represent a novel therapeutic strategy to promote axonal growth and regeneration. CI - Copyright (c) 2014 the authors 0270-6474/14/349281-09$15.00/0. FAU - Martinez, Jennifer AU - Martinez J AD - Department of Biological Sciences, Hunter College, New York, New York 10065, and Department of Pharmacology and. FAU - Stessin, Alexander M AU - Stessin AM AD - Department of Pharmacology and Stitch Radiation Oncology Department, Weill Cornell Medical College, New York, New York 10065. FAU - Campana, Aline AU - Campana A AD - Department of Biological Sciences, Hunter College, New York, New York 10065, and. FAU - Hou, Jianwei AU - Hou J AD - Department of Biological Sciences, Hunter College, New York, New York 10065, and. FAU - Nikulina, Elena AU - Nikulina E AD - Department of Pharmacology and. FAU - Buck, Jochen AU - Buck J AUID- ORCID: 0000-0002-3568-5869 AD - Department of Pharmacology and. FAU - Levin, Lonny R AU - Levin LR AD - Department of Pharmacology and llevin@med.cornell.edu. FAU - Filbin, Marie T AU - Filbin MT AD - Department of Biological Sciences, Hunter College, New York, New York 10065, and. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Myelin Proteins) RN - 0 (Myelin-Associated Glycoprotein) RN - EC 4.6.1.1 (Adenylyl Cyclases) SB - IM MH - Adenylyl Cyclases/*chemistry/*metabolism MH - Animals MH - Axons/*physiology/*ultrastructure MH - CHO Cells MH - Cell Enlargement MH - Cells, Cultured MH - Cerebellum/*metabolism/ultrastructure MH - Cricetulus MH - Enzyme Activation MH - Mice MH - Mice, Knockout MH - Myelin Proteins/*metabolism MH - Myelin-Associated Glycoprotein MH - Nerve Regeneration/*physiology MH - Neurogenesis/physiology MH - Rats MH - Rats, Long-Evans MH - Solubility PMC - PMC4087207 OTO - NOTNLM OT - BDNF OT - axonal regeneration OT - cAMP OT - soluble adenylyl cyclase EDAT- 2014/07/11 06:00 MHDA- 2014/09/10 06:00 PMCR- 2015/01/09 CRDT- 2014/07/11 06:00 PHST- 2014/07/11 06:00 [entrez] PHST- 2014/07/11 06:00 [pubmed] PHST- 2014/09/10 06:00 [medline] PHST- 2015/01/09 00:00 [pmc-release] AID - 34/28/9281 [pii] AID - 1434-14 [pii] AID - 10.1523/JNEUROSCI.1434-14.2014 [doi] PST - ppublish SO - J Neurosci. 2014 Jul 9;34(28):9281-9. doi: 10.1523/JNEUROSCI.1434-14.2014.