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.


Pat Hofer , Tamara Fitzinger , Marlene Fischer , Denise Slenter , and Eric Weitz


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Homo sapiens



Disease Ontology

neurodegenerative disease Parkinson's disease frontotemporal dementia amyotrophic lateral sclerosis Alzheimer's disease

Pathway 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-secretase
Activation 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


  1. 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
  2. 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