Involvement of δ-secretase in neurodegenerative diseases (WP5372)
Homo sapiens
Mammalian asparagine endopeptidase, also known as δ-secretase, is a key player in a number of neurodegenerative illnesses, including Alzheimer's, Parkinson's or ALS. The enzyme can get activated in the aging brain and starts to cleave amyloid precursor protein (APP) and promotes the production of amyloid-β (Aβ). δ-secretase also breaks down tau, alpha-synuclein, SET, and TAR DNA-binding protein 43, generating neurotoxic fragments and impairing their physiological processes. Each fragment has either been identified in patient samples with the relevant disease or has undergone testing to determine whether it can cause the disease pathology. This pathway is based on Figure 1 from the paper:"δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities. Published by Zhang Z, Tian Y, Ye K.
Authors
Pat Hofer , Tamara Fitzinger , Marlene Fischer , Denise Slenter , and Eric WeitzActivity
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Organisms
Homo sapiensCommunities
Annotations
Disease Ontology
neurodegenerative disease Parkinson's disease frontotemporal dementia amyotrophic lateral sclerosis Alzheimer's diseasePathway Ontology
amyotrophic lateral sclerosis pathway Alzheimer's disease pathway neurodegenerative pathway Parkinson's disease pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| Beta-amyloid | Metabolite | chebi:64645 | |
| Dopamine | Metabolite | chebi:18243 | |
| DOPAL | Metabolite | chebi:27978 | |
| LGMN | GeneProduct | ensembl:ENSG00000100600 | |
| BACE1 | GeneProduct | uniprot:P56817 | |
| AKT 2 | Protein | uniprot:P31751 | |
| Prolegumain | Protein | uniprot:Q99538 | Precursor of δ-secretaseActivation by self-cleavage |
| Microtubule-associated protein tau | Protein | uniprot:P10636 | |
| δ-secretase | Protein | uniprot:Q99538 | Phosphorylated |
| APP | Protein | uniprot:P05067 | |
| PP2A | Protein | uniprot:P62714 | Activated |
| STAT1 | Protein | uniprot:P42224 | |
| TrkB | Protein | uniprot:Q16620 | |
| BDNF | Protein | uniprot:P23560 | |
| SET | Protein | uniprot:Q01105 | |
| AKT 3 | Protein | uniprot:Q9Y243 | |
| Microtubule-associated protein tau | Protein | uniprot:P10636 | Phosphorylated |
| δ-secretase | Protein | uniprot:Q99538 | |
| C/EBP10A𝛽 | Protein | uniprot:P17676 | Only a part of the protein (less amino acids) |
| TDP-43 | Protein | uniprot:Q13148 | |
| MAO B | Protein | uniprot:P27338 | |
| α-synuclein | Protein | uniprot:P37840 | |
| SRPK2 | Protein | uniprot:P78362 | |
| AKT 1 | Protein | uniprot:P31749 | |
| PP2A | Protein | uniprot:P62714 | |
| AKT 1 | Protein | uniprot:P31749 | Phosphorylated |
| AKT 2 | Protein | uniprot:P31751 | Phosphorylated |
| AKT 3 | Protein | uniprot:Q9Y243 | Phosphorylated |
References
- How it all started: tau and protein phosphatase 2A. Liu C, Götz J. J Alzheimers Dis. 2013;37(3):483–94. PubMed Europe PMC Scholia
- δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities. Zhang Z, Tian Y, Ye K. Transl Neurodegener. 2020 Jan 6;9:1. PubMed Europe PMC Scholia