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p(HGNC:CASP3)

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Entity

Name
CASP3
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 12

Proteolytic processing of Alzeimer's beta-amyloid precursor protein v1.0.1

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing v1.0.0

Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease v1.0.0

Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies v1.0.0

Extracellular Tau and Its Potential Role in the Propagation of Tau Pathology v1.0.0

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Inflammasome Involvement in Alzheimer’s Disease v1.0.0

Amyloid-Binding Alcohol Dehydrogenase (ABAD) Inhibitors for the Treatment of Alzheimer’s Disease v1.0.0

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

Extracellular low-n oligomers of tau cause selective synaptotoxicity without affecting cell viability v1.0.0

Carboxy terminus heat shock protein 70 interacting protein reduces tau-associated degenerative changes v1.0.0

Tau in physiology and pathology v1.0.0

In-Edges 14

a(HBP:HBP00069) increases act(p(HGNC:CASP3)) View Subject | View Object

However, C31, a short form of AICD generated by caspase cleavage, has been reported to directly activate caspase 3 in the tumor cell death process (Lu et al. 2000; Bertrand et al. 2001; Nishimura et al. 2002; Madeira et al. 2005) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(CHEBI:spermidine) decreases act(p(HGNC:CASP3)) View Subject | View Object

Spermidine inhibits the acetylation of ATG7 and histone H3, while induc- ing beclin 1 via blockade of its cleavage by caspase 3 (REF.168) . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Machado-Joseph Disease

a(CHEBI:epoxomicin) increases act(p(HGNC:CASP3)) View Subject | View Object

Thrombin signaling can also activate caspases (36). Proteasomal impairment appears to be upstream of caspase activation, as inhibiting the proteasome with epoxomicin (EPX) led to activation of caspase-3 in primary neurons (63) and in a neuroblastoma cell line expressing wild-type tau (64). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

composite(p(HBP:"amyloid-beta oligomers"), p(HGNC:CASP3)) hasComponent p(HGNC:CASP3) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation act(p(HGNC:CASP3)) View Subject | View Object

In order for caspase to cleave tau in the AD brain, it needs to be present in its active form. The active forms of both caspase-3 and caspase-6 are elevated in AD-specific brain regions (temporal and frontal lobes) compared to unaffected regions (cerebellum) and control brains (57, 58). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Frontal Lobe
MeSH
Temporal Lobe
Text Location
Review

a(CHEBI:"methylene blue") decreases act(p(HGNC:CASP3)) View Subject | View Object

MB is a phenothiazine that crosses the blood brain barrier and acts as a redox cycler. Moreover, besides its beneficial properties as being able to improve energy metabolism and to act as an antioxidant, it is also able to reduce tau protein aggregation PubMed:26751493

Appears in Networks:

act(p(FPLX:JNK)) association p(HGNC:CASP3) View Subject | View Object

Overexpression of wild-type UNC5C causes low-grade death, intensified by an AD-linked mutation T835M inhibited by a AD-linked survival factor, calmodulin-like skin protein (CLSP), and a natural ligand of UNC5C, netrin1. T835M-UNC5C-induced neuronal cell death is mediated by an intracellular death-signaling cascade, consisting of DAPK1/protein kinase D/apoptosis signal-regulating kinase 1 (ASK1)/JNK/NADPH oxidase/caspases, which merges at ASK1 with a death-signaling cascade, mediated by amyloid ß precursor protein (APP). PubMed:27068745

Appears in Networks:

act(p(HGNC:MAP3K5)) association p(HGNC:CASP3) View Subject | View Object

Overexpression of wild-type UNC5C causes low-grade death, intensified by an AD-linked mutation T835M inhibited by a AD-linked survival factor, calmodulin-like skin protein (CLSP), and a natural ligand of UNC5C, netrin1. T835M-UNC5C-induced neuronal cell death is mediated by an intracellular death-signaling cascade, consisting of DAPK1/protein kinase D/apoptosis signal-regulating kinase 1 (ASK1)/JNK/NADPH oxidase/caspases, which merges at ASK1 with a death-signaling cascade, mediated by amyloid ß precursor protein (APP). PubMed:27068745

Appears in Networks:

a(CHEBI:"nitric oxide") increases act(p(HGNC:CASP3)) View Subject | View Object

NO can also bring about apoptosis of hippocampal neurons via caspase- 3 activity [50] whereas astrocyte-secreted IL-1 beta can increase the production of APP and A beta from neu- rons [51–53] (Fig. 1). PubMed:27314526

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus
MeSH
Alzheimer Disease
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph
NeuroMMSigDB
Nitric oxide subgraph

complex(p(HGNC:APP), p(HGNC:HSD17B10)) increases act(p(HGNC:CASP3)) View Subject | View Object

In another study, neurons from Tg mAPP/ABAD mice were shown to exhibit decreased activity of cyclooxygenase (COX) enzyme, spontaneous release of ROS, loss of mitochondrial membrane potential, a decrease in ATP production and release of cytochrome c from mitochondria with subsequent induction of caspase-3-like activity followed by apoptotic cell death. PubMed:30444369

Appears in Networks:
Annotations
MeSH
Neurons

p(HBP:"Tau oligomers", var("p.Lys280del")) increases act(p(HGNC:CASP3)) View Subject | View Object

To address this question, we first applied the oligomers directly after the purification of the protein eluting from the Butyl FF 16/ 10 column (without buffer exchange; 1, 5, and 10 mM) to SHSY5Y cells and observed a variety of toxic effects, including pronounced reduction in the cell viability (by MTT assay, Fig. 3A), increase in apoptotic cells (by Hoechst staining, Supplementary Fig. 4A), loss of mitochondrial membrane potential (by JC1 assay, Supplementary Fig. 4B), caspase 3/7 activation (Supplementary Fig. 4C-D), and cytochrome-c release (Supplementary Fig. 4), within 5 hours of incubation. PubMed:28528849

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SK-N-SH

p(HGNC:STUB1) regulates act(p(HGNC:CASP3)) View Subject | View Object

CHIP is also implicated in regulation of Caspase 3 activity PubMed:25374103

Appears in Networks:

p(HBP:"Tau C3") positiveCorrelation act(p(HGNC:CASP3)) View Subject | View Object

Tau overexpression increased active caspase 3 levels, and co-expression of CHIP reduced cleaved caspase 3 levels compared to tau expression alone (Fig. 3). PubMed:25374103

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)") positiveCorrelation act(p(HGNC:CASP3)) View Subject | View Object

Tau overexpression increased active caspase 3 levels, and co-expression of CHIP reduced cleaved caspase 3 levels compared to tau expression alone (Fig. 3). PubMed:25374103

Appears in Networks:

Out-Edges 17

act(p(HGNC:CASP3)) increases p(HGNC:BECN1, frag("?")) View Subject | View Object

Spermidine inhibits the acetylation of ATG7 and histone H3, while induc- ing beclin 1 via blockade of its cleavage by caspase 3 (REF.168) . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Machado-Joseph Disease

act(p(HGNC:CASP3)) increases p(HGNC:MAPT, frag("?_*")) View Subject | View Object

There is significant evidence that tau is a caspase substrate and that caspase-mediated tau cleavage may play a role in AD pathology. Early in vitro studies demonstrated that tau is cleaved in the C-terminus by several caspases including caspase-3 and caspase-6 (21–23). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

act(p(HGNC:CASP3)) increases deg(p(HGNC:MAPT)) View Subject | View Object

There may be reciprocity with the apoptosis pathway as activating caspase-3 by inducing apoptosis in cortical neuronal culture led to tau cleavage (22), and selectively expressing tauC3 led to apoptosis in NT2 and COS cells (21). This might represent a feed-forward loop of neurotoxicity. PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

act(p(HGNC:CASP3)) increases p(HBP:"Tau C3") View Subject | View Object

There may be reciprocity with the apoptosis pathway as activating caspase-3 by inducing apoptosis in cortical neuronal culture led to tau cleavage (22), and selectively expressing tauC3 led to apoptosis in NT2 and COS cells (21). This might represent a feed-forward loop of neurotoxicity. PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

act(p(HGNC:CASP3)) increases p(HBP:"Tau C3") View Subject | View Object

Caspase cleavage of tau may play a role in stimulating the tau aggregation seen in AD. Indeed, in vitro polymerization assays demonstrate that caspase-cleaved tau has a greater propensity to aggregate compared to full-length tau (23, 55). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

act(p(HGNC:CASP3)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

In order for caspase to cleave tau in the AD brain, it needs to be present in its active form. The active forms of both caspase-3 and caspase-6 are elevated in AD-specific brain regions (temporal and frontal lobes) compared to unaffected regions (cerebellum) and control brains (57, 58). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Frontal Lobe
MeSH
Temporal Lobe
Text Location
Review

act(p(HGNC:CASP3)) increases p(HGNC:MAPT) View Subject | View Object

Furthermore, caspase-3 cleavage at D421 increases tau release PubMed:29238289

Appears in Networks:

p(HGNC:CASP3) association act(p(FPLX:JNK)) View Subject | View Object

Overexpression of wild-type UNC5C causes low-grade death, intensified by an AD-linked mutation T835M inhibited by a AD-linked survival factor, calmodulin-like skin protein (CLSP), and a natural ligand of UNC5C, netrin1. T835M-UNC5C-induced neuronal cell death is mediated by an intracellular death-signaling cascade, consisting of DAPK1/protein kinase D/apoptosis signal-regulating kinase 1 (ASK1)/JNK/NADPH oxidase/caspases, which merges at ASK1 with a death-signaling cascade, mediated by amyloid ß precursor protein (APP). PubMed:27068745

Appears in Networks:

p(HGNC:CASP3) association act(p(HGNC:MAP3K5)) View Subject | View Object

Overexpression of wild-type UNC5C causes low-grade death, intensified by an AD-linked mutation T835M inhibited by a AD-linked survival factor, calmodulin-like skin protein (CLSP), and a natural ligand of UNC5C, netrin1. T835M-UNC5C-induced neuronal cell death is mediated by an intracellular death-signaling cascade, consisting of DAPK1/protein kinase D/apoptosis signal-regulating kinase 1 (ASK1)/JNK/NADPH oxidase/caspases, which merges at ASK1 with a death-signaling cascade, mediated by amyloid ß precursor protein (APP). PubMed:27068745

Appears in Networks:

p(HGNC:CASP3) increases bp(GO:"neuron apoptotic process") View Subject | View Object

Overexpression of wild-type UNC5C causes low-grade death, intensified by an AD-linked mutation T835M inhibited by a AD-linked survival factor, calmodulin-like skin protein (CLSP), and a natural ligand of UNC5C, netrin1. T835M-UNC5C-induced neuronal cell death is mediated by an intracellular death-signaling cascade, consisting of DAPK1/protein kinase D/apoptosis signal-regulating kinase 1 (ASK1)/JNK/NADPH oxidase/caspases, which merges at ASK1 with a death-signaling cascade, mediated by amyloid ß precursor protein (APP). PubMed:27068745

Appears in Networks:

act(p(HGNC:CASP3)) increases bp(GO:"neuron death") View Subject | View Object

NO can also bring about apoptosis of hippocampal neurons via caspase- 3 activity [50] whereas astrocyte-secreted IL-1 beta can increase the production of APP and A beta from neu- rons [51–53] (Fig. 1). PubMed:27314526

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus
MeSH
Alzheimer Disease
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph
NeuroMMSigDB
Nitric oxide subgraph

p(HGNC:CASP3) increases p(HGNC:BECN1, frag("?")) View Subject | View Object

For example, levels of Beclin 1, a key component of the class III type phosphoinositide 3-kinase/VPS34 complex essential to the pre-autophagosomal structure (PAS), has been suggested to be reduced in AD brains [16,17], with Rohn et al. demonstrating the cleavage of Beclin 1 by caspase-3 in the AD brain and colocalization of the cleaved product with NFTs [16]. PubMed:29758300

Appears in Networks:
Annotations
MeSH
Brain

p(HGNC:CASP3) hasVariant p(HGNC:CASP3, frag("?")) View Subject | View Object

Appears in Networks:

act(p(HGNC:CASP3)) positiveCorrelation p(HBP:"Tau isoform F (441 aa)") View Subject | View Object

Tau overexpression increased active caspase 3 levels, and co-expression of CHIP reduced cleaved caspase 3 levels compared to tau expression alone (Fig. 3). PubMed:25374103

Appears in Networks:

act(p(HGNC:CASP3)) positiveCorrelation p(HBP:"Tau C3") View Subject | View Object

Tau overexpression increased active caspase 3 levels, and co-expression of CHIP reduced cleaved caspase 3 levels compared to tau expression alone (Fig. 3). PubMed:25374103

Appears in Networks:

p(HGNC:CASP3) increases p(HGNC:MAPT, frag("?")) View Subject | View Object

For instance, the phosphorylation of tau at Ser422 inhibits the cleavage of tau by caspase 3 at Asp421 PubMed:26631930

Appears in Networks:

p(HGNC:CASP3) increases p(HGNC:MAPT, frag("1_421")) View Subject | View Object

In human AD brains and in the Tg4510 tauopathy mouse model, full-length tau is cleaved by caspase 3 behind Asp421 to generate tau1–421, which is prone to aggregation and subsequent formation of NFTs PubMed:26631930

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.