ADAM23 Gene

ADAM23 Gene[@yan2019]

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ADAM23 Gene</th>
</tr>
<tr>
<td class="label">Identifier</td>
<td>Value</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ADAM23</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ADAM metallopeptidase domain 23[@zhang2018]</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5385</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>603346</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000108439</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O75077</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>2q33.3</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebral Cortex</td>
<td>High</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Subventricular Zone</td>
<td>High</td>
</tr>
<tr>
<td class="label">Olfactory Bulb</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Thalamus</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Basal Ganglia</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Domain</td>
</tr>
<tr>
<td class="label">**Integrins (αvβ3, α5β

ADAM23 Gene[@yan2019]

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ADAM23 Gene</th>
</tr>
<tr>
<td class="label">Identifier</td>
<td>Value</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ADAM23</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ADAM metallopeptidase domain 23[@zhang2018]</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5385</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>603346</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000108439</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O75077</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>2q33.3</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebral Cortex</td>
<td>High</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Subventricular Zone</td>
<td>High</td>
</tr>
<tr>
<td class="label">Olfactory Bulb</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Thalamus</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Basal Ganglia</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Domain</td>
</tr>
<tr>
<td class="label">Integrins (αvβ3, α5β1, α6β1)</td>
<td>Disintegrin</td>
</tr>
<tr>
<td class="label">ADAM11</td>
<td>Disintegrin</td>
</tr>
<tr>
<td class="label">ADAM22</td>
<td>Disintegrin</td>
</tr>
<tr>
<td class="label">APP/APLP family</td>
<td>Unknown</td>
</tr>
<tr>
<td class="label">PSD-95</td>
<td>Cytoplasmic</td>
</tr>
<tr>
<td class="label">Grb2</td>
<td>Cytoplasmic</td>
</tr>
<tr>
<td class="label">p130Cas</td>
<td>Cytoplasmic</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

ADAM23 (A Disintegrin And Metalloproteinase domain 23) is a catalytically inactive member of the ADAM family expressed primarily in the brain. Located on chromosome 2q33.3, ADAM23 plays critical roles in neuronal development, synaptic function, and cell-cell adhesion, with emerging associations to [Alzheimer's Disease](/diseases/alzheimers-disease) (AD) and [Parkinson's Disease](/diseases/parkinsons-disease) (PD)[1][2][3].

Unlike catalytically active ADAMs, ADAM23 functions primarily as a regulator of cell adhesion and signaling through its disintegrin and cysteine-rich domains. This "ligand" role allows ADAM23 to modulate interactions between neurons and their environment without direct proteolytic activity, making it a unique target for understanding neurodevelopment and neurodegeneration[4][5].

Gene and Protein Structure

Gene Location and Organization

The ADAM23 gene is located at chromosome 2q33.3, spanning approximately 15 kb of genomic DNA. Key identifiers include:

The gene consists of 24 exons encoding a type I transmembrane protein. The genomic region shows evolutionary conservation, particularly in the disintegrin and cysteine-rich domains[1].

Protein Domain Architecture

ADAM23 contains the characteristic ADAM family domains, but with key differences due to its catalytic inactivity:

Signal Prodomain Metalloproteinase Disintegrin Cysteine-rich Transmembrane Cytoplasmic
peptide (inactive) domain region domain tail
↓ ↓ ↓ ↓ ↓ ↓ ↓
[1-19] [20-213] [214-463] [464-596] [597-666] [667-689] [690-834]

• Proline-rich regions (PXXP motifs) for SH3 domain binding
• Potential phosphorylation sites
• PDZ domain-binding motif at C-terminus

Biological Functions

Cell Adhesion

ADAM23 functions as a key mediator of cell-cell and cell-matrix adhesion in the nervous system[7][8]:

Integrin Interactions

The disintegrin domain of ADAM23 interacts with multiple integrin subunits:

• αvβ3: Vitronectin receptor expressed on neurons and glia
• α5β1: Fibronectin receptor
• α6β1: Laminin receptor
• α3β1: Collagen/laminin receptor

• Neuronal migration during development
• Axon guidance and fasciculation
• Synapse formation and maintenance
• Glial-neuronal interactions

Homophilic and Heterophilic Interactions

ADAM23 can engage in:

• Homophilic interactions: ADAM23-ADAM23 binding on adjacent cells
• Heterophilic interactions: Binding to other ADAM family members (e.g., ADAM11, ADAM22)
• Heterodimer formation: Complex formation with other disintegrin-containing proteins

Neuronal Migration

During cortical development, ADAM23 regulates neuronal migration through multiple mechanisms[9]:

The disintegrin domain mediates interactions with the extracellular matrix and neighboring cells, providing guidance cues for migrating neurons.

Synaptic Function

ADAM23 localizes to synaptic membranes where it plays critical roles in synaptic formation, maintenance, and plasticity[10]:

Synapse Formation

• Recruits synaptic adhesion molecules to nascent synapses
• Promotes dendritic spine formation
• Facilitates presynaptic terminal differentiation

Synaptic Maintenance

• Stabilizes synaptic contacts through adhesion interactions
• Regulates synaptic protein composition
• Maintains spine morphology

Synaptic Plasticity

• Modulates activity-dependent structural changes
• Influences LTP (long-term potentiation)
• Affects learning and memory processes

Signal Transduction

ADAM23 participates in multiple signaling pathways:

Expression Pattern

Developmental Expression

ADAM23 exhibits dynamic expression patterns during development:

• Embryonic day 12-14 (E12-E14): Low expression in neural tube
• E15-E18: Increasing expression in cortical plate
• Postnatal day 0-7 (P0-P7): Peak expression in cortex and hippocampus
• P14-P21: Gradual decline to adult levels

Adult Brain Expression

In the adult brain, ADAM23 expression is highest in:

Cellular Localization

• Neurons: Predominantly in soma and dendrites, enriched in dendritic spines
• Astrocytes: Limited expression, primarily at astrocyte-neuron interfaces
• Neural stem cells: High expression in subventricular zone progenitors
• Oligodendrocytes: Very low or absent

Disease Associations

Alzheimer's Disease

ADAM23 has emerged as a gene of interest in AD pathogenesis through multiple mechanisms[3][11][12]:

Altered Expression

• Reduced ADAM23 expression in AD brain tissue (particularly in hippocampus and cortex)
• Correlation between ADAM23 levels and disease severity
• Expression changes in early vs. late AD stages

Synaptic Dysfunction

ADAM23 localizes to synaptic membranes where it may regulate:

Amyloid Processing

While not directly involved in [amyloid precursor protein](/proteins/app) (APP) processing:

• ADAM23 may influence [amyloid-beta](/proteins/amyloid-beta) (Aβ) toxicity through synaptic effects
• Interactions with APP family proteins (APLP1, APLP2) are under investigation
• May affect neuronal vulnerability to Aβ-induced toxicity

Tau Pathology

Emerging evidence suggests potential interactions with [tau protein](/proteins/tau) pathology[13]:

• ADAM23 expression correlates with tau burden in some studies
• May affect tau-induced synaptic dysfunction
• Potential involvement in tau propagation mechanisms

Epigenetic Regulation

Studies reveal ADAM23 promoter methylation changes in AD[14]:

• Hypermethylation associated with reduced expression
• Potential use as epigenetic biomarker
• Links to AD-related transcriptional dysregulation

Parkinson's Disease

ADAM23 involvement in PD is an emerging area of research[15]:

Dopaminergic Neurons

• Altered ADAM23 expression in substantia nigra dopaminergic neurons
• Potential role in dopaminergic neuron survival
• May affect vulnerability to PD-related stress

Alpha-Synuclein Interactions

• Possible interactions with [alpha-synuclein](/proteins/alpha-synuclein) aggregation
• Effects on Lewy body formation
• May influence prion-like propagation

Neuroinflammation

• ADAM23 in microglial-neuronal communication
• Potential modulation of neuroinflammatory responses

Neurodevelopmental Disorders

ADAM23 mutations and dysregulation are associated with:

Cancer

Interestingly, ADAM23 functions as a tumor suppressor in some contexts:

• Reduced expression in gliomas
• Epigenetic silencing in certain cancers
• Potential prognostic value

Molecular Interactions

Protein Partners

ADAM23 interacts with numerous proteins to mediate its functions[17]:

Signaling Networks

ADAM23 integrates into cellular signaling networks:

Therapeutic Potential

Biomarker Applications

ADAM23 has potential as a disease biomarker:

• Altered levels in AD and PD
• Potential for disease diagnosis
• Correlation with disease progression

• Exosomal ADAM23
• Peripheral blood monocyte expression

Therapeutic Targets

ADAM23-based therapeutic strategies include:

Drug Development Challenges

• Brain penetration required
• Selectivity for ADAM23 vs. other ADAMs
• Maintaining proper folding and trafficking

Animal Models

Knockout Mice

ADAM23 global knockout:

• Viable but with neurological phenotypes
• Impaired spatial learning and memory
• Altered synaptic plasticity
• Abnormal cortical development in some models

Transgenic Models

• ADAM23 overexpression: Enhanced synaptic function
• Reporter lines: Visualization of ADAM23 expression patterns
• Conditional knockouts: Cell-type-specific deletion

Disease Models

• ADAM23 in APP/PS1 mice: Crosses with AD models
• ADAM23 in α-synuclein models: PD-related studies

Research Directions

Current Priorities

Emerging Techniques

• Single-cell RNA-seq to characterize ADAM23 expression
• Cryo-EM to determine ADAM23 structure
• CRISPR screening to identify genetic interactions
• Patient-derived iPSC neurons for disease modeling

Cross-Links

• [Alzheimer's Disease](/diseases/alzheimers-disease) - Primary disease context
• [Parkinson's Disease](/diseases/parkinsons-disease) - Related disease
• [Neurons](/entities/neurons) - Primary cell type
• [Astrocytes](/entities/astrocytes) - Supporting cell type
• [Hippocampus](/brain-regions/hippocampus) - Key brain region
• [Cortex](/brain-regions/cortex) - Key brain region
• [ADAM10 Gene](/genes/adam10) - Related ADAM family member
• [ADAM17 Gene](/genes/adam17) - Related ADAM family member
• [Tau Protein](/proteins/tau) - Related protein in AD
• [Alpha-Synuclein](/proteins/alpha-synuclein) - Related protein in PD

Summary

ADAM23 is a catalytically inactive ADAM family member with critical functions in the developing and adult nervous system. Through its disintegrin and cysteine-rich domains, ADAM23 mediates cell-cell and cell-matrix adhesion, regulates neuronal migration and cortical development, and plays essential roles in synaptic formation and plasticity. Altered ADAM23 expression in Alzheimer's and Parkinson's disease suggests potential involvement in neurodegeneration, though the precise mechanisms remain under investigation. As a non-proteolytic ADAM, ADAM23 offers unique opportunities for therapeutic targeting through modulation of adhesion-based signaling rather than catalytic activity.

Mechanism Map

References