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Appears in Networks 1

In-Edges 6

a(CHEBI:"calcium(2+)") increases act(p(HGNCGENEFAMILY:Calpains)) View Subject | View Object

Calpains are calcium-activated cytosolic cysteine proteases. Two isoforms differentiated and named by their sensitivities to calcium (i.e., μ-calpain and m-calpain, also called calpain-1 and calpain-2) are abundant in the central nervous system, and respond to micromolar and millimolar concentrations of calcium, respectively (45). Calpain has been implicated in a number of neurodegenerative diseases [for a review, see (46)]. PubMed:24027553

a(CHEBI:"calcium(2+)", loc(GO:intracellular)) increases act(p(HGNCGENEFAMILY:Calpains)) View Subject | View Object

Excitotoxicity leading to elevated intracellular calcium is a common feature of neurodegenerative diseases, and is implicated in AD (49, 50). This process may lead to enhanced activation of calpains (51). This in turn could influence a number of pathologic processes, including tau proteolysis. Indeed, tau has a number of putative calpain cleavage sites, and incubation of recombinant tau with calpain generates specific fragments, including one that is ∼35 kDa and one that is ∼17 kDa (19, 20). PubMed:24027553

a(CHEBI:"calcium(2+)", loc(GO:intracellular)) increases act(p(HGNCGENEFAMILY:Calpains)) View Subject | View Object

Increasing intracellular calcium levels in PC12 cells leads to calpain-induced cleavage of tau (18). This may reflect a potential effect of excitotoxicity in AD. Inducing apoptosis in cerebellar granule cells yields calpain-mediated tau fragments, including a dominant ∼17 kDa fragment (17). PubMed:24027553

Annotations
Experimental Factor Ontology (EFO)
PC12
Text Location
Review

a(CHEBI:"calpain inhibitor") decreases act(p(HGNCGENEFAMILY:Calpains)) View Subject | View Object

Also, treating primary hippocampal neurons with pre-aggregated amyloid beta (Abeta) led to the generation of tau fragments of ∼35, ∼24, and ∼17 kDa, which was blocked by addition of a calpain inhibitor (52, 53). Tau fragments of the same size were also found in AD brain tissue (19). PubMed:24027553

a(HBP:Excitotoxicity) association act(p(HGNCGENEFAMILY:Calpains)) View Subject | View Object

Increasing intracellular calcium levels in PC12 cells leads to calpain-induced cleavage of tau (18). This may reflect a potential effect of excitotoxicity in AD. Inducing apoptosis in cerebellar granule cells yields calpain-mediated tau fragments, including a dominant ∼17 kDa fragment (17). PubMed:24027553

Annotations
Experimental Factor Ontology (EFO)
PC12
Text Location
Review

path(MESH:"Neurodegenerative Diseases") association p(HGNCGENEFAMILY:Calpains) View Subject | View Object

Calpains are calcium-activated cytosolic cysteine proteases. Two isoforms differentiated and named by their sensitivities to calcium (i.e., μ-calpain and m-calpain, also called calpain-1 and calpain-2) are abundant in the central nervous system, and respond to micromolar and millimolar concentrations of calcium, respectively (45). Calpain has been implicated in a number of neurodegenerative diseases [for a review, see (46)]. PubMed:24027553

Out-Edges 11

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

Also of importance is understanding the role of non-degradative cleavage in influencing the eventual clearance of tau. Numerous proteases have been shown to proteolyze tau including aminopeptidases (10–12), thrombin (13–15), human high temperature requirement serine protease A1 (HTRA1) (16), calpain (17–20), and caspases (21–24). PubMed:24027553

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

Excitotoxicity leading to elevated intracellular calcium is a common feature of neurodegenerative diseases, and is implicated in AD (49, 50). This process may lead to enhanced activation of calpains (51). This in turn could influence a number of pathologic processes, including tau proteolysis. Indeed, tau has a number of putative calpain cleavage sites, and incubation of recombinant tau with calpain generates specific fragments, including one that is ∼35 kDa and one that is ∼17 kDa (19, 20). PubMed:24027553

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

Increasing intracellular calcium levels in PC12 cells leads to calpain-induced cleavage of tau (18). This may reflect a potential effect of excitotoxicity in AD. Inducing apoptosis in cerebellar granule cells yields calpain-mediated tau fragments, including a dominant ∼17 kDa fragment (17). PubMed:24027553

Annotations
Experimental Factor Ontology (EFO)
PC12
Text Location
Review

p(HGNCGENEFAMILY:Calpains) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

Calpains are calcium-activated cytosolic cysteine proteases. Two isoforms differentiated and named by their sensitivities to calcium (i.e., μ-calpain and m-calpain, also called calpain-1 and calpain-2) are abundant in the central nervous system, and respond to micromolar and millimolar concentrations of calcium, respectively (45). Calpain has been implicated in a number of neurodegenerative diseases [for a review, see (46)]. PubMed:24027553

act(p(HGNCGENEFAMILY:Calpains)) increases p(HGNC:MAPT, frag("?", "35kD")) View Subject | View Object

Excitotoxicity leading to elevated intracellular calcium is a common feature of neurodegenerative diseases, and is implicated in AD (49, 50). This process may lead to enhanced activation of calpains (51). This in turn could influence a number of pathologic processes, including tau proteolysis. Indeed, tau has a number of putative calpain cleavage sites, and incubation of recombinant tau with calpain generates specific fragments, including one that is ∼35 kDa and one that is ∼17 kDa (19, 20). PubMed:24027553

act(p(HGNCGENEFAMILY:Calpains)) increases p(HGNC:MAPT, frag("?", "17kD")) View Subject | View Object

Excitotoxicity leading to elevated intracellular calcium is a common feature of neurodegenerative diseases, and is implicated in AD (49, 50). This process may lead to enhanced activation of calpains (51). This in turn could influence a number of pathologic processes, including tau proteolysis. Indeed, tau has a number of putative calpain cleavage sites, and incubation of recombinant tau with calpain generates specific fragments, including one that is ∼35 kDa and one that is ∼17 kDa (19, 20). PubMed:24027553

act(p(HGNCGENEFAMILY:Calpains)) increases p(HGNC:MAPT, frag("?", "17kD")) View Subject | View Object

Increasing intracellular calcium levels in PC12 cells leads to calpain-induced cleavage of tau (18). This may reflect a potential effect of excitotoxicity in AD. Inducing apoptosis in cerebellar granule cells yields calpain-mediated tau fragments, including a dominant ∼17 kDa fragment (17). PubMed:24027553

Annotations
Experimental Factor Ontology (EFO)
PC12
Text Location
Review

act(p(HGNCGENEFAMILY:Calpains)) association a(HBP:Excitotoxicity) View Subject | View Object

Increasing intracellular calcium levels in PC12 cells leads to calpain-induced cleavage of tau (18). This may reflect a potential effect of excitotoxicity in AD. Inducing apoptosis in cerebellar granule cells yields calpain-mediated tau fragments, including a dominant ∼17 kDa fragment (17). PubMed:24027553

Annotations
Experimental Factor Ontology (EFO)
PC12
Text Location
Review

act(p(HGNCGENEFAMILY:Calpains)) increases path(HBP:Neurodegeneration) View Subject | View Object

On the one hand, expressing a 17-kDa fragment of tau based on calpain cleavage site mapping in hippocampal neurons led to neurite retraction and the appearance of varicosities after 48 h (52). Additionally, suppressing calpain activity in a fly model of tauopathy prevented neurodegeneration, as did expressing a calpain-resistant form of tau (54). PubMed:24027553

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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.