gene 1,033 words KG: ent-gene-6900b2bc
Contents

ADAMTS4 Gene

🧬 Gene Info
Gene Symbolent-gene-6900b2bc
Extracellular matrix (ECM) remodelingADAMTS-4 cleaves aggrecan and other proteoglycans (versican, brevican, neurocan) in the ECM, facilitating tissue remodeling during development and repair
Perineuronal net (PNN) degradationCleaves brevican and other chondroitin sulfate proteoglycans (CSPGs) that form PNNs, structures critical for synaptic stability and neural plasticity
Amyloid-beta clearanceIdentified as an amyloid-beta (Aβ)-degrading enzyme that can cleave Aβ peptides, potentially contributing to amyloid homeostasis in the brain
Neuroinflammatory modulationExpression is upregulated in reactive astrocytes and microglia during neuroinflammation
Spinal cord plasticityPromotes axonal regeneration and plasticity after spinal cord injury by degrading inhibitory CSPGs
Amyloid-beta degradationADAMTS-4 cleaves Aβ at multiple sites within the peptide, representing a novel Aβ-degrading pathway complementary to neprilysin and insulin-degrading enzyme
Protective variant mechanismThe protective I72V variant increases ADAMTS-4 enzymatic activity, enhancing Aβ clearance and reducing amyloid plaque burden in mouse models
Perineuronal net disruptionDysregulated ADAMTS-4 activity in AD may contribute to PNN breakdown, destabilizing synaptic connections and accelerating tau pathology spread
Reactive astrocyte expressionADAMTS4 is highly upregulated in disease-associated astrocytes surrounding amyloid plaques, suggesting a role in the glial response to Aβ deposition
High expressionCerebral cortex, hippocampus (particularly CA1 and dentate gyrus), striatum
Moderate expressionThalamus, cerebellum, brainstem, spinal cord
Cellular expressionPrimarily astrocytes, with lower expression in neurons and oligodendrocytes
Disease-state upregulationDramatically increased in reactive astrocytes near amyloid plaques in AD brain tissue
Subcellular localizationSecreted enzyme; localized to the extracellular space and cell surface
KG Connections2 knowledge graph edges
DatabasesGeneCardsUniProtNCBI GeneHPASTRING

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