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10.1523/JNEUROSCI.4808-14.2015 http://scihub22266oqcxt.onion/10.1523/JNEUROSCI.4808-14.2015 C4478251!4478251 !26109656     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 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\26109656 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Neurosci 2015 ; 35 (25 ): 9315-28 Nephropedia Template TP {{tp|p=26109656 |t=2015. The Progranulin Cleavage Products, Granulins, Exacerbate TDP-43 Toxicity and Increase TDP-43 Levels |pdf=|usr=}}{{26109656 }} gab.com Text The Progranulin Cleavage Products, Granulins, Exacerbate TDP-43 Toxicity and Increase TDP-43 Levels JO: J Neurosci http://www.kidney.de/pget.php?&tw=1&pmid=26109656 #FOAvip Mutations in the human progranulin gene resulting in protein haploinsufficiency cause frontotemporal lobar degeneration with TDP-43 inclusions. Although progress has been made in understanding the normal functions of progranulin and TDP-43, the molecular interactions between these proteins remain unclear. Progranulin is proteolytically processed into granulins, but the role of granulins in the pathogenesis of neurodegenerative disease is unknown. We used a Caenorhabditis elegans model of neuronal TDP-43 proteinopathy to specifically interrogate the contribution of granulins to the neurodegenerative process. Complete loss of the progranulin gene did not worsen TDP-43 toxicity, whereas progranulin heterozygosity did. Interestingly, expression of individual granulins alone had little effect on behavior. In contrast, when granulins were coexpressed with TDP-43, they exacerbated its toxicity in a variety of behaviors including motor coordination. These same granulins increased TDP-43 levels via a post-translational mechanism. We further found that in human neurodegenerative disease subjects, granulin fragments accumulated specifically in diseased regions of brain. To our knowledge, this is the first demonstration of a toxic role for granulin fragments in a neurodegenerative disease model. These studies suggest that presence of cleaved granulins, rather than or in addition to loss of full-length progranulin, may contribute to disease in TDP-43 proteinopathies. Twit Text FOAVip The Progranulin Cleavage Products, Granulins, Exacerbate TDP-43 Toxicity and Increase TDP-43 Levels ????J Neurosci http://www.kidney.de/pget.php?&tw=1&pmid=26109656 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26109656 #FOAvip English Wikipedia <ref>{{Cite pmid|26109656 }}</ref> The Progranulin Cleavage Products, Granulins, Exacerbate TDP-43 Toxicity and Increase TDP-43 Levels #MMPMID26109656 Salazar DA ; Butler VJ ; Argouarch AR ; Hsu TY ; Mason A ; Nakamura A ; McCurdy H ; Cox D ; Ng R ; Pan G ; Seeley WW ; Miller BL ; Kao AW J Neurosci 2015[Jun]; 35 (25 ): 9315-28 PMID26109656 show ga Mutations in the human progranulin gene resulting in protein haploinsufficiency cause frontotemporal lobar degeneration with TDP-43 inclusions. Although progress has been made in understanding the normal functions of progranulin and TDP-43, the molecular interactions between these proteins remain unclear. Progranulin is proteolytically processed into granulins, but the role of granulins in the pathogenesis of neurodegenerative disease is unknown. We used a Caenorhabditis elegans model of neuronal TDP-43 proteinopathy to specifically interrogate the contribution of granulins to the neurodegenerative process. Complete loss of the progranulin gene did not worsen TDP-43 toxicity, whereas progranulin heterozygosity did. Interestingly, expression of individual granulins alone had little effect on behavior. In contrast, when granulins were coexpressed with TDP-43, they exacerbated its toxicity in a variety of behaviors including motor coordination. These same granulins increased TDP-43 levels via a post-translational mechanism. We further found that in human neurodegenerative disease subjects, granulin fragments accumulated specifically in diseased regions of brain. To our knowledge, this is the first demonstration of a toxic role for granulin fragments in a neurodegenerative disease model. These studies suggest that presence of cleaved granulins, rather than or in addition to loss of full-length progranulin, may contribute to disease in TDP-43 proteinopathies. |Animals [MESH] |Animals, Genetically Modified [MESH] |Caenorhabditis elegans [MESH] |DNA-Binding Proteins/*metabolism [MESH] |Disease Models, Animal [MESH] |Humans [MESH] |Immunoblotting [MESH] |Intercellular Signaling Peptides and Proteins/*metabolism [MESH] |Progranulins [MESH] |Real-Time Polymerase Chain Reaction [MESH] |TDP-43 Proteinopathies/*metabolism [MESH]The Progranulin Cleavage Products, Granulins, Exacerbate TDP-43 Toxici(epmc).pdf DeepDyve Pubget Overpricing