scholarly journals New technologies to introduce a catalytic function into antibodies: A unique human catalytic antibody light chain showing degradation of β-amyloid molecule along with the peptidase activity

2019 ◽  
Vol 1 (2) ◽  
pp. 93-104
Author(s):  
Emi Hifumi ◽  
Hiroaki Taguchi ◽  
Eiichi Toorisaka ◽  
Taizo Uda
2020 ◽  
Vol 6 (13) ◽  
pp. eaay6441
Author(s):  
Emi Hifumi ◽  
Hiroaki Taguchi ◽  
Haruna Tsuda ◽  
Tetsuro Minagawa ◽  
Tamami Nonaka ◽  
...  

Over thousands of monoclonal antibodies (mAbs) have been produced so far, and it would be valuable if these mAbs could be directly converted into catalytic antibodies. We have designed a system to realize the above concept by deleting Pro95, a highly conserved residue in CDR-3 of the antibody light chain. The deletion of Pro95 is a key contributor to catalytic function of the light chain. The S35 and S38 light chains have identical amino acid sequences except for Pro95. The former, with Pro95 did not show any catalytic activity, whereas the latter, without Pro95, exhibited peptidase activity. To verify the generality of this finding, we tested another light chain, T99wt, which had Pro95 and showed little catalytic activity. In contrast, a Pro95-deleted mutant enzymatically degraded the peptide substrate and amyloid-beta molecule. These two cases demonstrate the potential for a new method of creating catalytic antibodies from the corresponding mAbs.


2004 ◽  
Vol 86 (2) ◽  
pp. 217-225 ◽  
Author(s):  
Yukie Mitsuda ◽  
Emi Hifumi ◽  
Kumi Tsuruhata ◽  
Hiroko Fujinami ◽  
Naoki Yamamoto ◽  
...  

2002 ◽  
Vol 269 (1-2) ◽  
pp. 283-298 ◽  
Author(s):  
Emi Hifumi ◽  
Yukie Mitsuda ◽  
Kyoko Ohara ◽  
Taizo Uda

2015 ◽  
Vol 29 (6) ◽  
pp. 2347-2358 ◽  
Author(s):  
Emi Hifumi ◽  
Mitsue Arakawa ◽  
Shingo Matsumoto ◽  
Tatsuhiro Yamamoto ◽  
Yoshiki Katayama ◽  
...  

2013 ◽  
Vol 288 (27) ◽  
pp. 19558-19568 ◽  
Author(s):  
Emi Hifumi ◽  
Naoko Fujimoto ◽  
Mitsue Arakawa ◽  
Eri Saito ◽  
Shingo Matsumoto ◽  
...  

2005 ◽  
Vol 96 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Yukie Mitsuda ◽  
Kumi Tsuruhata ◽  
Emi Hifumi ◽  
Masahiro Takagi ◽  
Taizo Uda

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Thom S. Lysen ◽  
M. Arfan Ikram ◽  
Mohsen Ghanbari ◽  
Annemarie I. Luik

AbstractSleep and 24-h activity rhythm disturbances are associated with development of neurodegenerative diseases and related pathophysiological processes in the brain. We determined the cross-sectional relation of sleep and 24-h activity rhythm disturbances with plasma-based biomarkers that might signal neurodegenerative disease, in 4712 middle-aged and elderly non-demented persons. Sleep and activity rhythms were measured using the Pittsburgh Sleep Quality Index and actigraphy. Simoa assays were used to measure plasma levels of neurofilament light chain, and additionally β-amyloid 40, β-amyloid 42, and total-tau. We used linear regression, adjusting for relevant confounders, and corrected for multiple testing. We found no associations of self-rated sleep, actigraphy-estimated sleep and 24-h activity rhythms with neurofilament light chain after confounder adjustment and correction for multiple testing, except for a non-linear association of self-rated time in bed with neurofilament light chain (P = 2.5*10−4). Similarly, we observed no significant associations with β-amyloid 40, β-amyloid 42, and total-tau after multiple testing correction. We conclude that sleep and 24-h activity rhythm disturbances were not consistently associated with neuronal damage as indicated by plasma neurofilament light chain in this population-based sample middle-aged and elderly non-demented persons. Further studies are needed to determine the associations of sleep and 24-h activity rhythm disturbances with NfL-related neuronal damage.


FEBS Journal ◽  
2005 ◽  
Vol 272 (17) ◽  
pp. 4497-4505 ◽  
Author(s):  
Emi Hifumi ◽  
Kenji Hatiuchi ◽  
Takuro Okuda ◽  
Akira Nishizono ◽  
Yoshiko Okamura ◽  
...  

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