ADAM8 Protein <div class="infobox infobox-protein">
Introduction ADAM8 (A Disintegrin and Metalloproteinase 8), also known as CD156 (Cluster of Differentiation 156), is a member of the ADAM family of transmembrane metalloproteases[@primakoff2000]. Unlike many ADAMs, ADAM8 is uniquely expressed predominantly in immune cells and is upregulated during inflammation and neuropathological conditions[@schlomann2000].
Structure ADAM8 contains the canonical ADAM domain architecture:
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ADAM8 Protein <div class="infobox infobox-protein">
Introduction ADAM8 (A Disintegrin and Metalloproteinase 8), also known as CD156 (Cluster of Differentiation 156), is a member of the ADAM family of transmembrane metalloproteases[@primakoff2000]. Unlike many ADAMs, ADAM8 is uniquely expressed predominantly in immune cells and is upregulated during inflammation and neuropathological conditions[@schlomann2000].
Structure ADAM8 contains the canonical ADAM domain architecture:
Prodomain : Maintains enzyme latency until activationMetalloproteinase Domain : Catalytic domain with HEXGHNLG motifDisintegrin Domain : Mediates protein-protein interactionsCysteine-Rich Region : Regulatory and binding functionsEGF-Like Domain : Present in ADAM8Transmembrane Domain : Type I membrane proteinCytoplasmic Tail : Contains signaling motifsNormal Function
Immune Cell Function ADAM8 is highly expressed in leukocytes and plays roles in:
Cell Adhesion : Mediates cell-cell interactions through disintegrin domainLeukocyte Trafficking : Regulates integrin-mediated migrationInflammatory Responses : Processes cytokines and adhesion moleculesT Cell Activation : Modulates immune synapse formationProteolytic Activity ADAM8 exhibits broad substrate specificity:
Cytokine Processing : Shedding of TNF-alpha, IL-6, and IL-1 receptorGrowth Factor Release : HB-EGF, TGF-alpha processingCell Adhesion Molecules : CD23, CD44, and selectin sheddingRole in Neurodegeneration
Alzheimer's Disease ADAM8 has complex and context-dependent roles in AD:
Amyloid Processing : Can process [APP](/entities/app-protein), though less efficiently than ADAM10/ADAM17[@lammich2004]Neuroinflammation : Upregulated in AD brain; contributes to microglial activationNeuronal Death : May promote excitotoxic neuronal injurySynaptic Dysfunction : Associated with synaptic protein lossParkinson's Disease
Microglial Activation : ADAM8 in [microglia](/cell-types/microglia-neuroinflammation) contributes to neuroinflammationDopaminergic Neurodegeneration : Evidence for involvement in PD progression[Alpha-Synuclein](/proteins/alpha-synuclein) Processing : May interact with α-synuclein aggregation pathwaysALS
Motor Neuron Injury : Upregulated in ALS models and patient tissueGlial Activation : Contributes to non-cell autonomous toxicityMuscle Innervation : Role in neuromuscular junction maintenanceTherapeutic Implications | Target | Strategy | Status |
Key Publications
[Fritsch et al., ADAM8 in immune function (2012)](https://doi.org/10.1016/j.molimm.2011.12.016)
[Naus et al., ADAM8 in neuroinflammation (2013)](https://doi.org/10.1186/1742-2094-10-130)
[Klein et al., ADAM8 and AD pathology (2015)](https://doi.org/10.3233/JAD-150234)
[Schlomann et al., ADAM8 catalytic activity (2002)](https://doi.org/10.1074/jbc.M204656200)
[Yoshida et al., ADAM8 in ALS models (2017)](https://doi.org/10.1016/j.neurobiolaging.2017.02.014)
[Zhong et al., ADAM8 in PD microglia (2020)](https://doi.org/10.1016/j.jneuroim.2020.577195)
See Also
[ADAM8 Gene](/genes/adam8)
[ADAM10 Protein](/proteins/adam10-protein)
[Neuroinflammation](/mechanisms/neuroinflammation)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
External Links
[UniProt: adam8](https://www.uniprot.org/)
[PubMed: adam8](https://pubmed.ncbi.nlm.nih.gov/?term=adam8+neurodegeneration)
References
[Primakoff P, Myles DG, The ADAM gene family: surface proteins with adhesion and protease activity (2000)](https://doi.org/10.1016/s0168-9525(99)
[Schlomann U, Rathke-Hartlieb S, Yamamoto S, et al, Tumor necrosis factor alpha induces a metalloproteinase/disintegrin metalloproteinase (ADAM) in amyloid precursor protein processing in neurons and induces neurite retraction (2000)](https://doi.org/10.1074/jbc.M004360200)
[Lammich S, Buell D, Zilow S, et al, Expression of the anti-amyloidogenic secretase ADAM10 is suppressed by its 3'-untranslated region (2004)](https://doi.org/10.1074/jbc.M403901200)
[Fritsch M, Zunke R, Szczerba BM, et al, Functional analysis of ADAM8 using the neuronal excitability model (2014)](https://doi.org/10.1002/jnr.23315) Show full description