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10.1021/jm3008618 http://scihub22266oqcxt.onion/10.1021/jm3008618 C4904786!4904786 !23013167     free     free     free Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 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\23013167 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Med+Chem 2012 ; 55 (21 ): 8997-9008 Nephropedia Template TP {{tp|p=23013167 |t=2012. Small-molecule structure correctors target abnormal protein structure and function: structure corrector rescue of apolipoprotein E4-associated neuropathology |pdf=|usr=}}{{23013167 }} gab.com Text Small-molecule structure correctors target abnormal protein structure and function: structure corrector rescue of apolipoprotein E4-associated neuropathology JO: J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=23013167 #FOAvip An attractive strategy to treat proteinopathies (diseases caused by malformed or misfolded proteins) is to restore protein function by inducing proper three-dimensional structure. We hypothesized that this approach would be effective in reversing the detrimental effects of apolipoprotein (apo) E4, the major allele that significantly increases the risk of developing Alzheimer's disease and other neurodegenerative disorders. ApoE4's detrimental effects result from its altered protein conformation ("domain interaction"), making it highly susceptible to proteolytic cleavage and the generation of neurotoxic fragments. Here, we review apoE structure and function and how apoE4 causes neurotoxicity, and describe the identification of potent small-molecule-based "structure correctors" that induce proper apoE4 folding. SAR studies identified a series of small molecules that significantly reduced apoE4's neurotoxic effects in cultured neurons and a series that reduced apoE4 fragment levels in vivo, providing proof-of-concept for our approach. Structure-corrector-based therapies could prove to be highly effective for the treatment of many protein-misfolding diseases. Twit Text FOAVip Small-molecule structure correctors target abnormal protein structure and function: structure corrector rescue of apolipoprotein E4-associated neuropathology ????J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=23013167 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=23013167 #FOAvip English Wikipedia <ref>{{Cite pmid|23013167 }}</ref> Small-molecule structure correctors target abnormal protein structure and function: structure corrector rescue of apolipoprotein E4-associated neuropathology #MMPMID23013167 Mahley RW ; Huang Y J Med Chem 2012[Nov]; 55 (21 ): 8997-9008 PMID23013167 show ga An attractive strategy to treat proteinopathies (diseases caused by malformed or misfolded proteins) is to restore protein function by inducing proper three-dimensional structure. We hypothesized that this approach would be effective in reversing the detrimental effects of apolipoprotein (apo) E4, the major allele that significantly increases the risk of developing Alzheimer's disease and other neurodegenerative disorders. ApoE4's detrimental effects result from its altered protein conformation ("domain interaction"), making it highly susceptible to proteolytic cleavage and the generation of neurotoxic fragments. Here, we review apoE structure and function and how apoE4 causes neurotoxicity, and describe the identification of potent small-molecule-based "structure correctors" that induce proper apoE4 folding. SAR studies identified a series of small molecules that significantly reduced apoE4's neurotoxic effects in cultured neurons and a series that reduced apoE4 fragment levels in vivo, providing proof-of-concept for our approach. Structure-corrector-based therapies could prove to be highly effective for the treatment of many protein-misfolding diseases. |Alzheimer Disease/drug therapy/metabolism [MESH] |Animals [MESH] |Apolipoprotein E4/chemistry/genetics/*metabolism [MESH] |Brain Injuries/metabolism [MESH] |Endoplasmic Reticulum/metabolism [MESH] |Golgi Apparatus/metabolism [MESH] |Humans [MESH] |Lipid Metabolism [MESH] |Models, Molecular [MESH] |Molecular Targeted Therapy [MESH] |Neurons/metabolism [MESH] |Protein Conformation [MESH] |Protein Folding/*drug effects [MESH] |Protein Transport [MESH] |Proteostasis Deficiencies/*drug therapy/metabolism [MESH]Small-molecule structure correctors target abnormal protein structure (epmc).pdf DeepDyve Pubget Overpricing