PSEN2

Understanding Entity Pages

This page aggregates everything SciDEX knows about PSEN2: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

Summary

Presenilin 2 (PSEN2) is a catalytic subunit of the gamma-secretase complex that cleaves APP to produce amyloid-beta peptides. Mutations in PSEN2 cause familial Alzheimer's disease with later onset (50-70 years) compared to PSEN1 mutations. PSEN2 mutations shift the Abeta42/Abeta40 ratio toward longer, more aggregation-prone peptides. Beyond APP cleavage, PSEN2 processes Notch, ErbB4, and other type I transmembrane proteins. PSEN2 also regulates calcium homeostasis in the endoplasmic reticulum and mitochondria-associated ER membranes (MAMs). PSEN2 is highly expressed in peripheral tissues as well as brain, suggesting systemic roles. The Volga German kindred carrying PSEN2 N141I provided early evidence linking presenilin mutations to familial AD.

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flowchart TD
    PSEN2["PSEN2<br/>(Presenilin 2)"]
    
    PSEN1["PSEN1<br/>(Presenilin 1)"]
    PEN2["PEN2<br/>(Gamma-secretase<br/>component)"]
    MAPT["MAPT<br/>(Tau protein)"]
    
    AmyloidBeta["Amyloid-beta<br/>(Abeta peptide)"]
    GammaSecretase["gamma-Secretase<br/>Complex"]
    
    EOAD["Early-onset<br/>Alzheimer's Disease"]
    AD["Alzheimer's<br/>Disease"]
    Neurodegeneration["Neurodegeneration"]
    
    AmyloidPlaques["Amyloid<br/>Plaques"]
    TauTangles["Tau<br/>Tangles"]
    
    A2M["A2M<br/>(Alpha-2-Macroglobulin)"]
    DHCR24["DHCR24<br/>(Cholesterol<br/>synthesis)"]
    PARP1["PARP1<br/>(DNA repair)"]
    
    CognitiveDecline["Cognitive<br/>Decline"]
    Apoptosis["Neuronal<br/>Death"]
    
    PSEN2 --|"forms"|--> GammaSecretase
    PSEN1 --|"forms"|--> GammaSecretase
    PEN2 --|"forms"|--> GammaSecretase
    
    PSEN2 --|"regulates"|--> AmyloidBeta
    GammaSecretase --|"cleaves APP to produce"|--> AmyloidBeta
    
    PSEN2 --|"activates"|--> MAPT
    MAPT --|"forms"|--> TauTangles
    
    PSEN2 --|"causes"|--> EOAD
    PSEN2 --|"causes"|--> AD
    AmyloidBeta --|"aggregates into"|--> AmyloidPlaques
    
    AmyloidPlaques --|"leads to"|--> Neurodegeneration
    TauTangles --|"leads to"|--> Neurodegeneration
    Neurodegeneration --|"results in"|--> CognitiveDecline
    Neurodegeneration --|"results in"|--> Apoptosis
    
    A2M --|"interacts with"|--> PSEN2
    DHCR24 --|"interacts with"|--> PSEN2
    PARP1 --|"interacts with"|--> PSEN2
    
    style PSEN2 fill:#006494
    style AmyloidBeta fill:#ef5350
    style EOAD fill:#5d4400
    style AD fill:#5d4400
    style Neurodegeneration fill:#ef5350
    style AmyloidPlaques fill:#ef5350
    style TauTangles fill:#ef5350
    style CognitiveDecline fill:#5d4400
    style Apoptosis fill:#ef5350
    style PSEN1 fill:#4a1a6b
    style PEN2 fill:#4a1a6b
    style MAPT fill:#4a1a6b
    style A2M fill:#1b5e20
    style DHCR24 fill:#4a1a6b
    style PARP1 fill:#1b5e20