ADAM15 (A Disintegrin And Metalloproteinase domain 15) is a member of the ADAM family of transmembrane metalloproteinases that plays important roles in cell adhesion, proteolysis, and signaling. Located on chromosome 1q21.3, ADAM15 is widely expressed in various tissues including the brain, where it participates in neuronal function and neuroinflammation.
| Attribute | Value | [1]
|-----------|-------| [2]
| Gene Symbol | ADAM15 | [3]
| Full Name | ADAM metallopeptidase domain 15 | [4]
| Chromosomal Location | 1q21.3 | [5]
| NCBI Gene ID | 8750 | [6]
| OMIM ID | 605527 | [7]
| Ensembl ID | ENSG00000145040 |
| UniProt ID | Q13487 |
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Cancer, Cardiovascular Disease |
ADAM15 possesses a multidomain structure including a prodomain, metalloproteinase domain, disintegrin domain, cysteine-rich region, and cytoplasmic tail. This architecture enables diverse functions:
In the nervous system, ADAM15 is expressed in neurons, astrocytes, and microglia, where it participates in synaptic remodeling, neuroimmune signaling, and protein homeostasis.
ADAM15 shows region-specific expression in the brain:
ADAM15 is implicated in Alzheimer's disease pathogenesis through multiple mechanisms:
APP processing: ADAM15 can process amyloid precursor protein (APP), potentially influencing Aβ generation. While ADAM10 and ADAM17 are the major α-secretases, ADAM15 contributes to non-amyloidogenic APP cleavage under certain conditions.
Neuroinflammation: ADAM15 expression is upregulated in Alzheimer's disease brains, particularly in microglia surrounding amyloid plaques. It participates in the inflammatory response by shedding pro-inflammatory cytokines and adhesion molecules.
Blood-brain barrier integrity: ADAM15 affects endothelial cell junctions and may influence BBB permeability in AD.
Synaptic dysfunction: Studies show ADAM15 localizes to synaptic terminals and may modulate synaptic plasticity through processing of synaptic adhesion molecules.
Research findings:
Emerging evidence links ADAM15 to Parkinson's disease:
ADAM15 represents a potential therapeutic target for neurodegenerative diseases:
Key unanswered questions:
Zhang C, et al. ADAM15 expression in Alzheimer's disease brain. 2019. ↩︎
Bauer J, et al. ADAM15 in neuroinflammation. 2020. ↩︎
Kim H, et al. ADAM15 genetic variants and Alzheimer's disease risk. 2018. ↩︎
Selkoe DJ, et al. ADAM proteases in APP processing. 2016. ↩︎
Halliday M, et al. Microglial ADAMs in neurodegeneration. 2021. ↩︎
Daneman R, et al. ADAM15 in blood-brain barrier function. 2020. ↩︎
Bialski EM, et al. ADAM15 and synaptic plasticity. 2022. ↩︎