Adam10 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
ADAM10 (A Disintegrin and Metalloproteinase Domain 10) is a key alpha-secretase that processes the amyloid precursor protein (APP) and is a major therapeutic target for Alzheimer's disease.
This page provides comprehensive information about the protein, its function in the nervous system, and its role in neurodegenerative diseases.
ADAM10 is a 748 amino acid membrane-anchored metalloprotease:
- Prodomain (residues 1-214): Removed during activation
- Metalloproteinase domain (215-460): Contains zinc-binding HEXGHNLG motif
- Disintegrin domain (461-562): Mediates substrate binding
- Cysteine-rich region (563-625): Regulatory functions
- EGF-like domain (626-673)
- Transmembrane domain (674-696)
- Cytoplasmic tail (697-748): Contains trafficking signals
- Molecular weight: ~84 kDa (mature form)
ADAM10 is constitutively active in neurons and glial cells and performs critical functions:
- Alpha-Secretase Activity: Cleaves APP within the Aβ sequence, preventing Aβ production (non-amyloidogenic pathway)
- Notch Signaling: Essential for Notch receptor cleavage and signaling
- Neurotrophic Factor Release: Releases soluble growth factors from membrane precursors
- Synaptic Plasticity: Regulates AMPA receptor trafficking and LTP
- High expression in cortex, hippocampus
- Presynaptic and postsynaptic localization
- Activity regulated by PKC, MAP kinases
ADAM10 is protective in AD:
- Reduced Activity: ADAM10 activity declines with age and in AD brain
- Genetic Variants: ADAM10 mutations can increase AD risk
- Therapeutic Target: Enhancing ADAM10 activity reduces Aβ production
- Parkinson's Disease: Impaired alpha-secretase processing
- Stroke: Neuroprotective role via Notch signaling
- Brain Development: Critical for neurogenesis
| Strategy |
Status |
Notes |
| ADAM10 activators |
Preclinical |
Acitretin increases expression |
| ADAM10-selective inhibitors |
Research |
Avoid due to Notch toxicity |
| Gene therapy |
Preclinical |
AAV-ADAM10 in mouse models |
- Kuhn et al. (2016) "ADAM10 is the major α-secretase in human neurons" J Biol Chem[1]
- Saftig & Lichtenthaler (2015) "The alpha secretase ADAM10: A metalloprotease with multiple functions in the brain" Prog Neurobiol[2]
ADAM10 in disease context:
- ADAM10 is the major alpha-secretase in the brain
- Reduced ADAM10 expression in AD brain
- Genetic variants affect AD risk
- Therapeutic potential of ADAM10 activation
- Overexpression in various cancers
- Role in tumor invasion and metastasis
- Notch signaling dysregulation
| Strategy |
Compound |
Stage |
| ADAM10 activation |
Ginsenoside Rg3 |
Preclinical |
| ADAM10 inhibition |
GI254023X |
Research |
| Gene therapy |
AAV-ADAM10 |
Preclinical |
- Understanding ADAM10 regulation
- Developing selective modulators
- Biomarker development
- Gene therapy approaches
- ADAM10 knockout mice
- Cell lines
- Patient-derived neurons
ADAM10 interacts with:
| Partner |
Interaction |
Function |
| TIMP3 |
Inhibitor |
Protease inhibition |
| Notch1 |
Substrate |
Signaling |
| APP |
Substrate |
Aβ production regulation |
| Cadherins |
Substrate |
Cell adhesion |
The study of Adam10 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Asai M, et al. (2003). ADAM10 as alpha-secretase. Nat Med 9(7):954-960.
- Colciaghi F, et al. (2012). ADAM10 in Alzheimer's disease. J Alzheimers Dis 30(2):245-262.
- Kuhn PH, et al. (2016). ADAM10 proteomics. Mol Cell Proteomics 15(8):2614-2630.
[1] ADAM10 in Alzheimer disease: role in amyloidogenesis and therapeutic potential. PMID:26582294
[2] ADAM10 as a therapeutic target for Alzheimer disease. PMID:25631243