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10.1038/srep43545 http://scihub22266oqcxt.onion/10.1038/srep43545 C5335257!5335257 !28256546     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28256546 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Sci+Rep 2017 ; 7 (ä): 43545 Nephropedia Template TP {{tp|p=28256546 |t=2017. Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis |pdf=|usr=}}{{28256546 }} gab.com Text Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis JO: Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=28256546 #FOAvip Multiple Sclerosis (MS) is a neurodegenerative disease where immune-driven demyelination occurs with inefficient remyelination, but therapies are limited, especially those to enhance repair. Here, we show that the dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, VP3.15, a heterocyclic small molecule with good pharmacokinetic properties and safety profile, improves in vivo remyelination in mouse and increases both adult mouse and adult human oligodendrocyte progenitor cell (OPC) differentiation, in addition to its immune regulatory action. The dual inhibition is synergistic, as increasing intracellular levels of cAMP by cyclic nucleotide PDE inhibition both suppresses the immune response and increases remyelination, and in addition, inhibition of GSK3 limits experimental autoimmune encephalomyelitis in mice. This combination of an advantageous effect on the immune response and an enhancement of repair, plus demonstration of its activity on adult human OPCs, leads us to propose dual PDE7-GSK3 inhibition, and specifically VP3.15, as a neuroprotective and neuroreparative disease-modifying treatment for MS. Twit Text FOAVip Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis ????Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=28256546 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28256546 #FOAvip English Wikipedia <ref>{{Cite pmid|28256546 }}</ref> Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis #MMPMID28256546 Medina-Rodríguez EM ; Bribián A ; Boyd A ; Palomo V ; Pastor J ; Lagares A ; Gil C ; Martínez A ; Williams A ; de Castro F Sci Rep 2017[Mar]; 7 (ä): 43545 PMID28256546 show ga Multiple Sclerosis (MS) is a neurodegenerative disease where immune-driven demyelination occurs with inefficient remyelination, but therapies are limited, especially those to enhance repair. Here, we show that the dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, VP3.15, a heterocyclic small molecule with good pharmacokinetic properties and safety profile, improves in vivo remyelination in mouse and increases both adult mouse and adult human oligodendrocyte progenitor cell (OPC) differentiation, in addition to its immune regulatory action. The dual inhibition is synergistic, as increasing intracellular levels of cAMP by cyclic nucleotide PDE inhibition both suppresses the immune response and increases remyelination, and in addition, inhibition of GSK3 limits experimental autoimmune encephalomyelitis in mice. This combination of an advantageous effect on the immune response and an enhancement of repair, plus demonstration of its activity on adult human OPCs, leads us to propose dual PDE7-GSK3 inhibition, and specifically VP3.15, as a neuroprotective and neuroreparative disease-modifying treatment for MS. |Animals [MESH] |Cell Differentiation/drug effects [MESH] |Cell Proliferation/drug effects [MESH] |Cell Survival/drug effects [MESH] |Cells, Cultured [MESH] |Cyclic Nucleotide Phosphodiesterases, Type 7/antagonists & inhibitors [MESH] |Disease Models, Animal [MESH] |Encephalomyelitis, Autoimmune, Experimental [MESH] |Enzyme Inhibitors/chemistry/*pharmacology/therapeutic use [MESH] |Glycogen Synthase Kinase 3/antagonists & inhibitors [MESH] |Humans [MESH] |Male [MESH] |Mice [MESH] |Multiple Sclerosis/drug therapy/*metabolism/pathology [MESH] |Myelin Sheath/*drug effects/*metabolism/pathology [MESH] |Oligodendroglia/cytology/drug effects/metabolism [MESH]Promoting in vivo remyelination with small molecules: a neuroreparativ(epmc).pdf DeepDyve Pubget Overpricing