Gene[ADAM8](/genes/adam8)
UniProt[O15230](https://www.uniprot.org/uniprot/O15230)
PDB Structures5FN5, 5FOC
Molecular Weight93.5 kDa (pro-form), 68 kDa (mature form)
Subcellular LocalizationPlasma membrane, Cell surface, Leukocyte granules
Protein FamilyADAM (A Disintegrin and Metalloproteinase) family
ADAM8 (A Disintegrin and Metalloproteinase 8), also known as CD156 (Cluster of Differentiation 156), is a member of the ADAM family of transmembrane metalloproteases. Unlike many ADAMs, ADAM8 is uniquely expressed predominantly in immune cells and is upregulated during inflammation and neuropathological conditions.
ADAM8 contains the canonical ADAM domain architecture:
- Prodomain: Maintains enzyme latency until activation
- Metalloproteinase Domain: Catalytic domain with HEXGHNLG motif
- Disintegrin Domain: Mediates protein-protein interactions
- Cysteine-Rich Region: Regulatory and binding functions
- EGF-Like Domain: Present in ADAM8
- Transmembrane Domain: Type I membrane protein
- Cytoplasmic Tail: Contains signaling motifs
ADAM8 is highly expressed in leukocytes and plays roles in:
- Cell Adhesion: Mediates cell-cell interactions through disintegrin domain
- Leukocyte Trafficking: Regulates integrin-mediated migration
- Inflammatory Responses: Processes cytokines and adhesion molecules
- T Cell Activation: Modulates immune synapse formation
ADAM8 exhibits broad substrate specificity:
- Cytokine Processing: Shedding of TNF-alpha, IL-6, and IL-1 receptor
- Growth Factor Release: HB-EGF, TGF-alpha processing
- Cell Adhesion Molecules: CD23, CD44, and selectin shedding
ADAM8 has complex and context-dependent roles in AD:
- Amyloid Processing: Can process APP, though less efficiently than ADAM10/ADAM17
- Neuroinflammation: Upregulated in AD brain; contributes to microglial activation
- Neuronal Death: May promote excitotoxic neuronal injury
- Synaptic Dysfunction: Associated with synaptic protein loss
- Microglial Activation: ADAM8 in microglia contributes to neuroinflammation
- Dopaminergic Neurodegeneration: Evidence for involvement in PD progression
- Alpha-Synuclein Processing: May interact with α-synuclein aggregation pathways
- Motor Neuron Injury: Upregulated in ALS models and patient tissue
- Glial Activation: Contributes to non-cell autonomous toxicity
- Muscle Innervation: Role in neuromuscular junction maintenance
| Target |
Strategy |
Status |
| ADAM8 Inhibition |
Monoclonal antibodies |
Preclinical |
| Metalloproteinase inhibition |
Broad-spectrum inhibitors |
Limited by toxicity |
| Gene silencing |
siRNA approaches |
Research |
- Fritsch et al., ADAM8 in immune function (2012)
- Naus et al., ADAM8 in neuroinflammation (2013)
- Klein et al., ADAM8 and AD pathology (2015)
- Schlomann et al., ADAM8 catalytic activity (2002)
- Yoshida et al., ADAM8 in ALS models (2017)
- Zhong et al., ADAM8 in PD microglia (2020)