Platelet coagulation factor XIa-inhibitor, a form of Alzheimer amyloid precursor protein

Science ◽  
1990 ◽  
Vol 248 (4959) ◽  
pp. 1126-1128 ◽  
Author(s):  
R. Smith ◽  
D. Higuchi ◽  
G. Broze
Keyword(s):  
Amyloid Precursor Protein ◽  
Coagulation Factor ◽  
Precursor Protein ◽  
Factor Xia

Binding of amyloid β precursor protein to coagulation factor XIa in vivo may favour haemorrhagic stroke

1998 ◽  
Vol 245 (2) ◽  
pp. 111-115 ◽  
Author(s):  
M. Bornebroek ◽  
Peter A. Kr. von dem Borne ◽  
Joost Haan ◽  
Joost C. M. Meijers ◽  
William E. Van Nostrand ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Coagulation Factor ◽  
Haemorrhagic Stroke ◽  
Precursor Protein ◽  
Factor Xia

Thrombin Induces Surface and Intracellular Secretion of Amyloid Precursor Protein from Human Endothelial Cells

1999 ◽  
Vol 81 (04) ◽  
pp. 630-637 ◽  
Author(s):  
John R. Ciallella ◽  
Helmer Figueiredo ◽  
Virginia Smith-Swintosky ◽  
Joseph P. McGillis
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Umbilical Vein ◽  
Calcium Ionophore ◽  
Coagulation Factor ◽  
Immunohistochemical Analysis ◽  
Precursor Protein ◽  
Thrombin Receptor ◽  
Umbilical Vein Endothelial Cells

SummaryThrombin, a major coagulant and inflammatory mediator, was shown to regulate amyloid precursor protein (APP) secretion. APP is the protein from which the amyloid beta peptide (Aß) is derived. Aß forms the core of vascular and cerebral plaques in Alzheimer’s disease (AD). In this study, human umbilical vein endothelial cells (HUVEC) were used to examine the effects of thrombin on APP expression. Cell supernatants from thrombin-treated HUVEC were immunoblotted to measure secreted APP. Thrombin-induced secretion of APP peaks at approximately 30 min post-treatment. Immunohistochemical analysis found that APP is not colocalized with or secreted through the same pathway as coagulation factor VIII. The secretion of APP is thrombin receptor-mediated, since it is inhibited by the thrombin antagonist N-Acetyl-D-Phe-Pro1Amido-4-Guanidino-Butyl-1-Boronic Acid. It also is induced by treatment with a calcium ionophore. Moreover, APP secretion is protein kinase C (PKC)-dependent because it is blocked by the PKC inhibitor bisindolylmaleimide. APP secretion also occurs from the cell surface, possibly through direct cleavage by thrombin. Immunoreactivity on the surface of HUVEC decreased after thrombin treatment but not after treatment with a non-proteolytic thrombin receptor activator. These data suggest that thrombin induces APP secretion through a PKC-dependent mechanism, as well as from the cell surface. Our results are consistent with thrombin playing a role in AD pathology.

Post-Translational Modifications of Platelet-Derived Amyloid Precursor Protein by Coagulation Factor XIII-A*

Biochemistry ◽  
2020 ◽  
Vol 59 (46) ◽  
pp. 4449-4455
Author(s):  
Woosuk S. Hur ◽  
Lih Jiin Juang ◽  
Nima Mazinani ◽  
Lonna Munro ◽  
Wilfred A. Jefferies ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Precursor Protein ◽  
Post Translational Modifications ◽  
Coagulation Factor Xiii

Memapsin 2, a drug target for Alzheimer's disease

2003 ◽  
Vol 70 ◽  
pp. 213-220 ◽  
Author(s):  
Gerald Koelsch ◽  
Robert T. Turner ◽  
Lin Hong ◽  
Arun K. Ghosh ◽  
Jordan Tang
Keyword(s):  
Crystal Structure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transition State ◽  
Amyloid Precursor Protein ◽  
Therapeutic Target ◽  
Drug Target ◽  
Aspartic Protease ◽  
Precursor Protein ◽  
Memapsin 2

Mempasin 2, a ϐ-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of ϐ-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been established and have led to the design of potent and relatively small transition-state inhibitors. Although developing a clinically viable mempasin 2 inhibitor remains challenging, progress to date renders hope that memapsin 2 inhibitors may ultimately be useful for therapeutic reduction of ϐ-amyloid.

Interplay between Pur α and Egr-1 in the transcriptional regulation of amyloid precursor protein gene expression

2010 ◽  
Vol 34 (8) ◽  
pp. S27-S27
Author(s):  
Jianqi Cui ◽  
Xiuying Pei ◽  
Qian Zhang ◽  
Bassel E. Sawaya ◽  
Xiaohong Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Amyloid Precursor Protein ◽  
Protein Gene ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Gene

Insulinrezeptorsubstrat (IRS)2-Expression moduliert die Amyloid-Precursor-Protein (APP) Spaltung in vivo

2010 ◽  
Vol 5 (S 01) ◽  
Author(s):  
M Udelhoven ◽  
T Ehlkes ◽  
MM Hettich ◽  
S Asrat ◽  
W Krone ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein

Structural and Dynamic Study of the Transmembrane Domain of the Amyloid Precursor Protein

Acta Naturae ◽  
2011 ◽  
Vol 3 (1) ◽  
pp. 69-76 ◽  
Author(s):  
K D Nadezhdin ◽  
O V Bocharova ◽  
E V Bocharov ◽  
A S Arseniev
Keyword(s):  
Amyloid Precursor Protein ◽  
Transmembrane Domain ◽  
Dynamic Study ◽  
Precursor Protein
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