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10.1194/jlr.R047381 http://scihub22266oqcxt.onion/10.1194/jlr.R047381 C4173992!4173992!24668939     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Lipid+Res 2014 ; 55 (10): 1996-2003 Nephropedia Template TP {{tp|p=24668939|t=2014. Development of targeted therapies for Parkinson?s disease and related synucleinopathies |pdf=|usr=}}{{24668939}} gab.com Text Development of targeted therapies for Parkinson s disease and related synucleinopathies JO: J Lipid Res http://www.kidney.de/pget.php?&tw=1&pmid=24668939 #FOAvip Therapeutic efforts in neurodegenerative diseases have been very challenging, particularly due to a lack of validated and mechanism-based therapeutic targets and biomarkers. The basic idea underlying the novel therapeutic approaches reviewed here is that by exploring the molecular basis of neurodegeneration in a rare lysosomal disease such as Gaucher?s disease (GD), new molecular targets will be identified for therapeutic development in common synucleinopathies. Accumulation of ?-synuclein plays a key role in the pathogenesis of Parkinson?s disease (PD) and other synucleinopathies, suggesting that improved clearance of ?-synuclein may be of therapeutic benefit. To achieve this goal, it is important to identify specific mechanisms and targets involved in the clearance of ?-synuclein. Recent discovery of clinical, genetic, and pathological linkage between GD and PD offers a unique opportunity to examine lysosomal glucocerebrosidase, an enzyme mutated in GD, for development of targeted therapies in synucleinopathies. While modulation of glucocerebrosidase and glycolipid metabolism offers a viable approach to treating disorders associated with synuclein accumulation, the compounds described to date either lack the ability to penetrate the CNS or have off-target effects that may counteract or limit their capabilities to mediate the desired pharmacological action. However, recent emergence of selective inhibitors of glycosphingolipid biosynthesis and noninhibitory pharmacological chaperones of glycosphingolipid processing enzymes that gain access to the CNS provide a novel approach that may overcome some of the limitations of compounds reported to date. These new strategies may allow for development of targeted treatments for synucleinopathies that affect both children and adults. Twit Text FOAVip Development of targeted therapies for Parkinson s disease and related synucleinopathies ????J Lipid Res http://www.kidney.de/pget.php?&tw=1&pmid=24668939 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24668939 #FOAvip English Wikipedia <ref>{{Cite pmid|24668939}}</ref> Development of targeted therapies for Parkinson?s disease and related synucleinopathies #MMPMID24668939 Sybertz E; Krainc D J Lipid Res 2014[Oct]; 55 (10): 1996-2003 PMID24668939show ga Therapeutic efforts in neurodegenerative diseases have been very challenging, particularly due to a lack of validated and mechanism-based therapeutic targets and biomarkers. The basic idea underlying the novel therapeutic approaches reviewed here is that by exploring the molecular basis of neurodegeneration in a rare lysosomal disease such as Gaucher?s disease (GD), new molecular targets will be identified for therapeutic development in common synucleinopathies. Accumulation of ?-synuclein plays a key role in the pathogenesis of Parkinson?s disease (PD) and other synucleinopathies, suggesting that improved clearance of ?-synuclein may be of therapeutic benefit. To achieve this goal, it is important to identify specific mechanisms and targets involved in the clearance of ?-synuclein. Recent discovery of clinical, genetic, and pathological linkage between GD and PD offers a unique opportunity to examine lysosomal glucocerebrosidase, an enzyme mutated in GD, for development of targeted therapies in synucleinopathies. While modulation of glucocerebrosidase and glycolipid metabolism offers a viable approach to treating disorders associated with synuclein accumulation, the compounds described to date either lack the ability to penetrate the CNS or have off-target effects that may counteract or limit their capabilities to mediate the desired pharmacological action. However, recent emergence of selective inhibitors of glycosphingolipid biosynthesis and noninhibitory pharmacological chaperones of glycosphingolipid processing enzymes that gain access to the CNS provide a novel approach that may overcome some of the limitations of compounds reported to date. These new strategies may allow for development of targeted treatments for synucleinopathies that affect both children and adults. äDevelopment of targeted therapies for Parkinson?s disease and related (epmc).pdf DeepDyve Pubget Overpricing