scholarly journals Rho‐associated coiled‐coil kinase 1 activation mediates amyloid precursor protein site‐specific Ser655 phosphorylation and triggers amyloid pathology

Aging Cell ◽  
2019 ◽  
Vol 18 (5) ◽  
Author(s):  
Yong‐Bo Hu ◽  
Ru‐Jing Ren ◽  
Yong‐Fang Zhang ◽  
Yue Huang ◽  
Hai‐Lun Cui ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Coiled Coil ◽  
Precursor Protein ◽  
Site Specific ◽  
Amyloid Pathology

TgCRND8 Amyloid Precursor Protein Transgenic Mice Exhibit an Altered γ-Secretase Processing and an Aggressive, Additive Amyloid Pathology Subject to Immunotherapeutic Modulation†

Biochemistry ◽  
2007 ◽  
Vol 46 (36) ◽  
pp. 10317-10327 ◽  
Author(s):  
Gregory D. Van Vickle ◽  
Chera L. Esh ◽  
Walter M. Kalback ◽  
R. Lyle Patton ◽  
Dean C. Luehrs ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Amyloid Pathology

Copper-Binding Amyloid Precursor Protein Undergoes a Site-Specific Fragmentation in the Reduction of Hydrogen Peroxide†

Biochemistry ◽  
1998 ◽  
Vol 37 (20) ◽  
pp. 7224-7230 ◽  
Author(s):  
Gerd Multhaup ◽  
Thomas Ruppert ◽  
Andrea Schlicksupp ◽  
Lars Hesse ◽  
Eckhard Bill ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Copper Binding ◽  
Site Specific ◽  
A Site

scholarly journals Dimeric Transmembrane Orientations of APP/C99 Regulate γ-Secretase Processing Line Impacting Signaling and Oligomerization

2020 ◽  
Author(s):  
Florian Perrin ◽  
Nicolas Papadopoulos ◽  
Rémi Opsomer ◽  
Devkee M. Vadukul ◽  
Céline Vrancx ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Gene Transcription ◽  
Coiled Coil ◽  
Precursor Protein ◽  
Aβ Peptide ◽  
Intracellular Domain ◽  
Mrna Induction ◽  
Amyloidogenic Processing ◽  
Processing Line ◽  
Cleavage Lines

AbstractAmyloid precursor protein (APP) cleavage by the β secretase produces the C99 transmembrane (TM) protein, which contains three dimerization-inducing Gly-x-x-x-Gly motifs. We demonstrate that dimeric C99 TM orientations regulate the precise cleavage lines by γ-secretase. Of all possible dimeric orientations imposed by a coiled coil to the C99 TM-cytosolic domain, the dimer (cc-del7) containing 33Gly-x-x-x-Gly37 in the interface promoted Aβ42 processing line and AICD (APP Intracellular Domain)-dependent gene transcription, including BACE1 mRNA induction, enhancing amyloidogenic signaling. Another orientation exhibiting 25Gly-x-x-x-Gly29 in the interface (cc-del6) favored processing to Aβ43/40, induced significantly less gene transcription, while promoting formation of SDS-resistant “Aβ-like” oligomers, reminiscent of Aβ peptide oligomers. These required both Val24 of a pro-β motif and the 25Gly-x-x-x-Gly29 interface. Thus, crossing angles imposed by dimeric orientations give access to γ-secretase at Aβ48 or Aβ49, linking the former to enhanced signaling and Aβ42. We discuss avenues of blocking amyloidogenic processing.

The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human β-amyloid precursor protein transgenic mice

2004 ◽  
Vol 25 (10) ◽  
pp. 1315-1321 ◽  
Author(s):  
Joo-Yong Lee ◽  
Jonathan E. Friedman ◽  
Itzchak Angel ◽  
Alex Kozak ◽  
Jae-Young Koh
Keyword(s):  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Metal Chelator ◽  
Amyloid Pathology ◽  
Β Amyloid
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