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](/entities/app-protein) (APP) and is a major therapeutic target for [Alzheimer's disease](/diseases/alzheimers-disease). [@colciaghi2012]
Overview
This page provides comprehensive information about the protein, its function in the nervous system, and its role in neurodegenerative diseases. [@kuhn2016]
Structure
ADAM10 is a 748 amino acid membrane-anchored metalloprotease:
Prodomain (residues 1-214): Removed during activation
ADAM10 is constitutively active in [neurons](/entities/neurons) and glial cells and performs critical functions:
Key Functions:
Alpha-Secretase Activity: Cleaves APP within the [Aβ](/proteins/amyloid-beta) sequence, preventing [Aβ](/proteins/amyloid-beta) 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](/mechanisms/long-term-potentiation)
Brain Expression:
High expression in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus)
Presynaptic and postsynaptic localization
Activity regulated by PKC, MAP kinases
Role in Disease
Alzheimer's Disease
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
Kuhn et al. (2016) "ADAM10 is the major α-secretase in human neurons" J Biol Chem[@asai2003]
Saftig & Lichtenthaler (2015) "The alpha secretase ADAM10: A metalloprotease with multiple functions in the brain" Prog Neurobiol[@colciaghi2012]
Clinical Significance
ADAM10 in disease context:
Alzheimer's Disease
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
Cancer
Overexpression in various cancers
Role in tumor invasion and metastasis
Notch signaling dysregulation
Therapeutic Approaches
Research Directions
Current Focus
Understanding ADAM10 regulation
Developing selective modulators
Biomarker development
Gene therapy approaches
Model Systems
ADAM10 knockout mice
Cell lines
Patient-derived neurons
Protein Interactions
ADAM10 interacts with:
Background
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.
References
<sup>[[1]](https://pubmed.ncbi.nlm.nih.gov/26582294/)</sup> ADAM10 in Alzheimer disease: role in amyloidogenesis and therapeutic potential. PMID: 26582294(https://pubmed.ncbi.nlm.nih.gov/26582294/)
<sup>[[2]](https://pubmed.ncbi.nlm.nih.gov/25631243/)</sup> ADAM10 as a therapeutic target for Alzheimer disease. PMID: 25631243(https://pubmed.ncbi.nlm.nih.gov/25631243/)