Literature summary for 3.4.21.69 extracted from

Wang, Y.; Zhao, Z.; Rege, S.V.; Wang, M.; Si, G.; Zhou, Y.; Wang, S.; Griffin, J.H.; Goldman, S.A.; Zlokovic, B.V.
3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice (2016), Nat. Med., 22, 1050-1055 .

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Application

Application	Comment	Organism
medicine	Recombinant APC and/or its analogues with reduced by over 90% anticoagulant activity such as mutant 3K3A-APC (K191A/K192A/K193A), engineered to reduce APC-associated bleeding risk while retaining normal cell signaling activity, have shown benefits in preclinical models of ischemic stroke, brain trauma, multiple sclerosis, amyotrophic lateral sclerosis, sepsis, ischemic/reperfusion injury of heart, kidney and liver, pulmonary, kidney and gastrointestinal inflammation, diabetes, and lethal body radiation. Enzyme mutant 3K3A-APC stimulates neuronal production by human neural stem/progenitor cells (NSCs) in vitro via a PAR1-PAR3-sphingosine-1-phosphate receptor 1-Akt pathway, suggesting the potential for APC-based treatment as a strategy for structural repair in the human central nervous system. Late post-ischemic treatment of C57BL/6J mice with 3K3A-APC stimulates neuronal production by transplanted human NSCs, promotes circuit restoration, and improves functional recovery	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
K191A/K192A/K193A	site-directed mutagenesis, the mutant is engineered to reduce APC-associated bleeding risk while retaining normal cell signaling activity. Enzyme mutant 3K3A-APC stimulates neuronal production by human neural stem/progenitor cells (NSCs) in vitro via a PAR1-PAR3-sphingosine-1-phosphate receptor 1-Akt pathway. Effects of late post-ischemic 3K3A-APC treatment on the in vivo production of neurons from transplanted NSCs in mice, and the effects of this combination therapy on long-term neurological recovery and restoration of disrupted neural circuitry in the post-ischemic murine brain, functional integration of NSCs into the host neuronal circuitry, overview	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P04070	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
fetus	fetal neural stem/progenitor cells	Homo sapiens	-
neural stem cell	-	Homo sapiens	-

Synonyms

Synonyms	Comment	Organism
Activated protein C	-	Homo sapiens
APC	-	Homo sapiens

General Information

General Information	Comment	Organism
physiological function	activated protein C (APC) is a blood protease with anticoagulant activity and cell-signaling activities mediated by activation of protease-activated receptors 1 and 3 (PAR1, PAR3) via non-canonical cleavage1. Recombinant APC and/or its analogues with reduced by over 90% anticoagulant activity such as mutant 3K3A-APC (K191A/K192A/K193A), engineered to reduce APC-associated bleeding risk while retaining normal cell signaling activity, have shown benefits in preclinical models of ischemic stroke, brain trauma, multiple sclerosis, amyotrophic lateral sclerosis, sepsis, ischemic/reperfusion injury of heart, kidney and liver, pulmonary, kidney and gastrointestinal inflammation, diabetes, and lethal body radiation. Enzyme mutant 3K3A-APC stimulates neuronal production by human neural stem/progenitor cells (NSCs) in vitro via a PAR1-PAR3-sphingosine-1-phosphate receptor 1-Akt pathway. Effects of late post-ischemic 3K3A-APC treatment on the in vivo production of neurons from transplanted NSCs in C57BL/6J mice, and the effects of this combination therapy on long-term neurological recovery and restoration of disrupted neural circuitry in the post-ischemic murine brain, functional integration of NSCs into the host neuronal circuitry, overview	Homo sapiens

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Release 2023.1 (January 2023)