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10.1007/s00401-018-1869-0 http://scihub22266oqcxt.onion/10.1007/s00401-018-1869-0 29934874/?report=reader!6112111!29934874     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 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       Acta+Neuropathol 2018 ; 136 (1): 69-87 Nephropedia Template TP {{tp|p=29934874|t=2018. Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders |pdf=|usr=}}{{29934874}} gab.com Text Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders JO: Acta Neuropathol http://www.kidney.de/pget.php?&tw=1&pmid=29934874 #FOAvip Alzheimer's disease (AD) is the most common form of dementia in the elderly affecting more than 5 million people in the U.S. AD is characterized by the accumulation of beta-amyloid (Abeta) and Tau in the brain, and is manifested by severe impairments in memory and cognition. Therefore, removing tau pathology has become one of the main therapeutic goals for the treatment of AD. Tau (tubulin-associated unit) is a major neuronal cytoskeletal protein found in the CNS encoded by the gene MAPT. Alternative splicing generates two major isoforms of tau containing either 3 or 4 repeat (R) segments. These 3R or 4RTau species are differentially expressed in neurodegenerative diseases. Previous studies have been focused on reducing Tau accumulation with antibodies against total Tau, 4RTau or phosphorylated isoforms. Here, we developed a brain penetrating, single chain antibody that specifically recognizes a pathogenic 3RTau. This single chain antibody was modified by the addition of a fragment of the apoB protein to facilitate trafficking into the brain, once in the CNS these antibody fragments reduced the accumulation of 3RTau and related deficits in a transgenic mouse model of tauopathy. NMR studies showed that the single chain antibody recognized an epitope at aa 40-62 of 3RTau. This single chain antibody reduced 3RTau transmission and facilitated the clearance of Tau via the endosomal-lysosomal pathway. Together, these results suggest that targeting 3RTau with highly specific, brain penetrating, single chain antibodies might be of potential value for the treatment of tauopathies such as Pick's Disease. Twit Text FOAVip Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders ????Acta Neuropathol http://www.kidney.de/pget.php?&tw=1&pmid=29934874 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29934874 #FOAvip English Wikipedia <ref>{{Cite pmid|29934874}}</ref> Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders #MMPMID29934874 Spencer B; Bruschweiler S; Sealey-Cardona M; Rockenstein E; Adame A; Florio J; Mante M; Trinh I; Rissman RA; Konrat R; Masliah E Acta Neuropathol 2018[Jul]; 136 (1): 69-87 PMID29934874show ga Alzheimer's disease (AD) is the most common form of dementia in the elderly affecting more than 5 million people in the U.S. AD is characterized by the accumulation of beta-amyloid (Abeta) and Tau in the brain, and is manifested by severe impairments in memory and cognition. Therefore, removing tau pathology has become one of the main therapeutic goals for the treatment of AD. Tau (tubulin-associated unit) is a major neuronal cytoskeletal protein found in the CNS encoded by the gene MAPT. Alternative splicing generates two major isoforms of tau containing either 3 or 4 repeat (R) segments. These 3R or 4RTau species are differentially expressed in neurodegenerative diseases. Previous studies have been focused on reducing Tau accumulation with antibodies against total Tau, 4RTau or phosphorylated isoforms. Here, we developed a brain penetrating, single chain antibody that specifically recognizes a pathogenic 3RTau. This single chain antibody was modified by the addition of a fragment of the apoB protein to facilitate trafficking into the brain, once in the CNS these antibody fragments reduced the accumulation of 3RTau and related deficits in a transgenic mouse model of tauopathy. NMR studies showed that the single chain antibody recognized an epitope at aa 40-62 of 3RTau. This single chain antibody reduced 3RTau transmission and facilitated the clearance of Tau via the endosomal-lysosomal pathway. Together, these results suggest that targeting 3RTau with highly specific, brain penetrating, single chain antibodies might be of potential value for the treatment of tauopathies such as Pick's Disease. |Alzheimer Disease/*drug therapy/genetics/pathology[MESH] |Animals[MESH] |Apolipoproteins B/metabolism[MESH] |Brain/drug effects/metabolism[MESH] |Cell Line, Transformed[MESH] |Coculture Techniques[MESH] |DNA Repeat Expansion/*genetics[MESH] |Disease Models, Animal[MESH] |Exploratory Behavior/drug effects[MESH] |Humans[MESH] |Mice[MESH] |Mice, Inbred C57BL[MESH] |Mice, Transgenic[MESH] |Microtubule-Associated Proteins/metabolism[MESH] |Neuroblastoma/pathology[MESH] |Phosphorylation[MESH] |Pick Disease of the Brain/*drug therapy/genetics/pathology[MESH] |Protein Transport/drug effects/genetics[MESH] |Single-Chain Antibodies/*therapeutic use[MESH] |rab5 GTP-Binding Proteins/metabolism[MESH]Selective targeting of 3 repeat Tau with brain penetrating single chai(epmc).pdf DeepDyve Pubget Overpricing