Involvement of δ-secretase in neurodegenerative diseases (Homo sapiens)

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1TDP-43: aggregationin inclusion bodiescleaved SRPK2 increasesnuclear translocationand kinase activity -> promoting tau aggregationaggregationSET fragment: hyperphosphorylation -> tau aggregationvia PP2A inhibitionphosphorylated by SRPK2:promote enzymatic activityTau (1-368) fragment:more prone to phosphorylationmore prone to aggreagation-> neurotoxic effectblocked TrkB -> increased delta-secretase expression,fragmentation of APP and tau,blockage of neuronal signals ->neuronal cell deathamyloid-beta promotes δ-secretase expressionphosphorylated by AKT:inhibit enzymatic activationSET fragmentα-synuclein (1-103) fragmentTDP-43 fragmentTrkBMicrotubule-associated protein tauδ-secretaseMAO BSETLGMNδ-secretaseBDNFC/EBP𝛽TDP-43BACE1mRNAdopamineTau (1-368) fragmentα-synucleinDOPALAPPSTAT1AKTMicrotubule-associated protein tauSRPK2beta-amyloidAKTSRPK2 fragmentPAP


Description

δ-secretase in neurodegenerative diseases.

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Quality Tags

Ontology Terms

 

Bibliography

  1. Zhang Z, Tian Y, Ye K; ''δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities.''; Transl Neurodegener, 2020 PubMed Europe PMC Scholia
  2. Liu C, Götz J; ''How it all started: tau and protein phosphatase 2A.''; J Alzheimers Dis, 2013 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
129533view01:28, 9 May 2024EweitzOntology Term : 'neuron' added !
128716view01:31, 21 February 2024EweitzOntology Term : 'neurodegenerative pathway' added !
128715view01:31, 21 February 2024EweitzOntology Term : 'amyotrophic lateral sclerosis pathway' added !
128714view23:11, 20 February 2024EweitzModified description
128713view23:09, 20 February 2024EweitzNote relation to Parkinson's disease, per source
128712view23:05, 20 February 2024EweitzNote relation to FTD and ALS, per source
128711view22:57, 20 February 2024EweitzNote relation to Alzheimer's disease, per source diagram
128710view22:53, 20 February 2024EweitzRefine interaction per source; refine metabolite name
128695view21:20, 19 February 2024EweitzRefine caption placement
128694view21:19, 19 February 2024EweitzFix typo, color metabolites blue, economize
126830view10:04, 26 June 2023Pat hoferchanged ID of phosphorylated delta-secretase
126826view19:39, 25 June 2023Pat hoferChanged arrows of phosphorylation-reactions to MIM-modification-interaction
126825view19:30, 25 June 2023Pat hoferChanged ID of delta-secretase, comments for prolegumain, added akt 1/2/3 as a group
126819view09:13, 25 June 2023Tamara FitzingerOntology Term : 'Parkinson's disease pathway' added !
126818view09:12, 25 June 2023Tamara FitzingerOntology Term : 'Alzheimer's disease pathway' added !
126779view13:44, 22 June 2023DeSlUpdated desription, removed comments with personal email details
126744view15:18, 16 June 2023Tamara FitzingerModified description
126743view15:04, 16 June 2023Pat hoferLiterature update
126741view14:27, 16 June 2023Pat hoferadded Prolegumain and Legumain
126740view14:02, 16 June 2023Marlenef97Modified description
126738view10:34, 16 June 2023Pat hofer
126737view09:05, 16 June 2023Pat hofer
126736view09:00, 16 June 2023Pat hofer
126735view08:56, 16 June 2023Pat hofer
126734view08:53, 16 June 2023Pat hoferchanged datasource of IDs, added PP2A, changed linestle of inhibition of tau phosphorylation
126716view12:13, 15 June 2023Pat hoferAdded IDs for Tau-protein and APP
126715view11:44, 15 June 2023Pat hofer
126714view11:41, 15 June 2023Pat hoferChanged Uniprot/Swiss IDs to Uniprot/Trembl IDs
126685view14:46, 12 June 2023Marlenef97
126669view07:46, 10 June 2023Pat hofer
126655view16:01, 9 June 2023Marlenef97- controlled all IDs

- located STAT1 and BACE1 in nucleus - changed interaction between amyloid-beta and sectretase to interaction between amyloid beta and LGMN - changed interaction of TrkB and C/EBP from mim-stimulation to mim-inhibition

- added comment
126640view11:14, 8 June 2023Pat hofer
126639view11:12, 8 June 2023Pat hofer
126638view10:55, 8 June 2023Pat hofer
126637view10:53, 8 June 2023Pat hofer
126636view10:51, 8 June 2023Pat hoferBibliography, cleavage arrows, protein-names, phosphorylation of d-secretase by SRPK2
126632view16:04, 7 June 2023Tamara Fitzinger
126624view15:23, 7 June 2023Tamara Fitzinger
126623view15:18, 7 June 2023Pat hoferAdded Bibliography
126622view15:14, 7 June 2023Tamara FitzingerOntology Term : 'frontotemporal dementia' added !
126621view15:14, 7 June 2023Tamara FitzingerOntology Term : 'amyotrophic lateral sclerosis' added !
126620view15:13, 7 June 2023Tamara FitzingerOntology Term : 'Alzheimer's disease' added !
126619view15:13, 7 June 2023Tamara FitzingerOntology Term : 'Parkinson's disease' added !
126618view15:11, 7 June 2023Tamara FitzingerOntology Term : 'neurodegenerative disease' added !
126617view15:08, 7 June 2023Marlenef97Modified description
126616view15:03, 7 June 2023Tamara FitzingerModified title
126615view15:01, 7 June 2023Pat hoferModified title
126614view14:54, 7 June 2023Pat hoferNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKTProteinA0A0U4CQG9 (Uniprot-TrEMBL) Activated
APPProteinP05067 (Uniprot-TrEMBL)
BACE1 GeneProductQ8IYC8 (Uniprot-TrEMBL)
BDNFProteinA0A0E3SU01 (Uniprot-TrEMBL)
C/EBP𝛽ProteinQ9BSC0 (Uniprot-TrEMBL) Only a part of the protein (less amino acids)
DOPALMetabolite27978 (ChEBI)
LGMNGeneProductENSG00000100600 (Ensembl)
MAO B ProteinQ8TBI1 (Uniprot-TrEMBL)
Microtubule-associated protein tauProteinP10636 (Uniprot-TrEMBL) Phosphorylated
SET fragmentProtein
SETProteinQ5VXV3 (Uniprot-TrEMBL)
SRPK2 fragmentProtein
SRPK2ProteinC9J2M4 (Uniprot-TrEMBL)
STAT1 ProteinA0A669KB68 (Uniprot-TrEMBL)
TDP-43 fragmentProtein
TDP-43ProteinA0A087WX29 (Uniprot-TrEMBL)
Tau (1-368) fragment Protein
TrkBProteinQ548C2 (Uniprot-TrEMBL)
beta-amyloidMetaboliteCHEBI:64645 (ChEBI)
dopamineMetaboliteCHEBI:18243 (ChEBI)
mRNARna
α-synuclein (1-103) fragmentProtein
α-synucleinProteinH6UYS5 (Uniprot-TrEMBL)
δ-secretase ProteinQ53XC6 (Uniprot-TrEMBL)
δ-secretaseProteinQ53XC6 (Uniprot-TrEMBL) Phosphorylated

Annotated Interactions

No annotated interactions

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