ADAM8

ADAM8 Full Name

ADAM metallopeptidase domain 8

ADAM8 Introduction

Overview of ADAM8
ADAM8 (A Disintegrin And Metalloprotease 8), also known as CD156a, is a member of the ADAM family of transmembrane glycoproteins that combine metalloprotease, disintegrin, and cysteine-rich domains. Expressed in a variety of tissues including immune cells, lung, kidney, and brain, ADAM8 plays a dual role as both a protease and a cell adhesion molecule. Unlike other ADAM family members, ADAM8 exhibits unique tissue-specific expression patterns and functional versatility, making it a key player in both physiological processes and pathological conditions.The ADAM8 protein consists of multiple conserved structural domains that enable its diverse biological functions. The N-terminal signal peptide directs its cellular localization, followed by a prodomain that regulates protease activation through cleavage. The catalytic metalloprotease domain contains the zinc-binding motif (HEXXHXXGXXHD) essential for proteolytic activity, while the disintegrin domain mediates cell-cell and cell-matrix interactions via integrin binding. Additional domains include a cysteine-rich region, an epidermal growth factor (EGF)-like domain, a transmembrane domain, and a cytoplasmic tail that modulates intracellular signaling pathways. Post-translational modifications such as glycosylation further fine-tune ADAM8 structure and function.

Figure 1.Synthesis and biological evaluation of analogues of the potent ADAM8 inhibitor cyclo(RLsKDK) for the treatment of inflammatory diseases. (Yim, Victor, et al.2016)

Physiological Functions of ADAM8
Under normal physiological conditions, ADAM8 contributes to critical biological processes including immune response regulation, tissue development, and cellular homeostasis. In the immune system, it modulates leukocyte migration and activation by cleaving cell surface molecules such as L-selectin and chemokines, thereby influencing inflammatory cell recruitment. During embryonic development, ADAM8 participates in tissue remodeling and cell migration events necessary for organogenesis. Additionally, ADAM8 plays a role in bone metabolism by regulating osteoclast differentiation and activity, and in neuronal development through modulation of cell adhesion and growth factor processing in the central nervous system.

Therapeutic Potential of Targeting ADAM8
Given its role in multiple diseases, ADAM8 has emerged as an attractive target for therapeutic intervention. Small molecule inhibitors of the ADAM8 metalloprotease domain have shown promise in preclinical models of cancer and inflammatory diseases, reducing tumor growth and inflammation without significant off-target effects. Monoclonal antibodies targeting ADAM8 either block its proteolytic activity or inhibit its cell adhesion functions, offering a more specific approach compared to broad-spectrum metalloprotease inhibitors. Additionally, antisense oligonucleotides and siRNA strategies have been developed to downregulate ADAM8 expression in disease-affected tissues. Ongoing research aims to optimize these therapeutic modalities for clinical use, with a focus on improving specificity and reducing systemic toxicity.

Alternate Names for ADAM8

ADAM8; ADAM metallopeptidase domain 8; a disintegrin and metalloproteinase domain 8; disintegrin and metalloproteinase domain-containing protein 8; CD156; MS2; A Disintegrin And Metalloproteinase domain 8; ADAM 8; ADAM 8 precursor; ADAM metallopeptidase d

• 3.Yim, Victor, et al. Synthesis and biological evaluation of analogues of the potent ADAM8 inhibitor cyclo (RLsKDK) for the treatment of inflammatory diseases and cancer metastasis. Bioorganic & Medicinal Chemistry. 2016, 24.18: 4032-4037.