TNN Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TNN Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>TNN</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Tenascin N</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>1q23.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[57123](https://www.ncbi.nlm.nih.gov/gene/57123)</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>[608581](https://www.omim.org/entry/608581)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q9C0B1](https://www.uniprot.org/uniprot/Q9C0B1)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000132604</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Tenascin</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~240 kDa</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
TNN (Tenascin N) encodes tenascin N, a member of the tenascin family of extracellular matrix (ECM) glycoproteins. Tenascins are large matricellular proteins that play critical roles in brain development, synaptic plasticity, and neural circuit formation. TNN is particularly expressed in the nervous system and has been implicated in various neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD).
Gene Overview
Background
...TNN Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TNN Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>TNN</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Tenascin N</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>1q23.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[57123](https://www.ncbi.nlm.nih.gov/gene/57123)</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>[608581](https://www.omim.org/entry/608581)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q9C0B1](https://www.uniprot.org/uniprot/Q9C0B1)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000132604</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Tenascin</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~240 kDa</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
TNN (Tenascin N) encodes tenascin N, a member of the tenascin family of extracellular matrix (ECM) glycoproteins. Tenascins are large matricellular proteins that play critical roles in brain development, synaptic plasticity, and neural circuit formation. TNN is particularly expressed in the nervous system and has been implicated in various neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD).
Gene Overview
Background
The tenascin family consists of four members in vertebrates: tenascin-C (TNC), tenascin-R (TNR), tenascin-X (TNXB), and tenascin-N (TNN). Unlike other tenascins, TNN has a restricted expression pattern primarily in the nervous system, where it is synthesized by [astrocytes](/entities/astrocytes) and certain neuronal populations during development and in adulthood.
TNN is characterized by a modular structure containing epidermal growth factor (EGF)-like repeats, fibronectin type III (FNIII) repeats, and a fibrinogen-like globe domain. This unique architecture allows TNN to interact with various cell surface receptors, including integrins and proteoglycans, mediating cell-ECM adhesion and signaling events crucial for neural circuit formation and maintenance.
Expression Pattern
Brain Regions
TNN expression in the brain is temporally regulated and region-specific:
- [Hippocampus](/brain-regions/hippocampus): TNN is expressed in the dentate gyrus and CA regions, particularly during synaptic plasticity
- Cerebral [Cortex](/brain-regions/cortex): Layer-specific expression in cortical [neurons](/entities/neurons), with higher levels in layer I
- Cerebellum: Present in the molecular layer and Purkinje cell layer
- Thalamus: Expression in specific thalamic nuclei
- Olfactory Bulb: Detected in the glomerular layer
Cellular Expression
- Astrocytes: Primary source of TNN in the adult brain
- Neurons: Subpopulations of excitatory and inhibitory neurons
- Oligodendrocyte Precursor Cells (OPCs): TNN expression during differentiation
Normal Function
TNN contributes to the formation and maintenance of the extracellular matrix in the central nervous system (CNS). It interacts with other ECM components, including fibronectin, laminin, and proteoglycans, to create a permissive environment for neurite outgrowth and synapse formation.
Synaptic Function
TNN plays important roles in synaptic development and plasticity:
Synaptogenesis: TNN accumulates at synaptic sites during development and regulates the formation of both excitatory and inhibitory synapses
Synaptic Stability: Maintains synaptic structure through interactions with postsynaptic density proteins
Plasticity: Involved in activity-dependent synaptic remodeling
Neurotransmitter Receptor Clustering: Facilitates the organization of glutamate and GABA receptors at synapsesAxon Guidance
During development, TNN acts as a guidance cue for growing axons, repelling certain neuronal populations and attracting others through interactions with cell surface receptors.
Glial-Neuronal Interactions
TNN mediates communication between astrocytes and neurons, supporting metabolic coupling and information processing in neural circuits.
Disease Associations
Alzheimer's Disease (AD)
TNN has been implicated in Alzheimer's disease pathogenesis through multiple mechanisms:
- Amyloid Interaction: TNN can bind to [amyloid-beta](/proteins/amyloid-beta) (Aβ) peptides and may influence Aβ aggregation and deposition
- Synaptic Loss: Altered TNN expression in AD brains correlates with synaptic degeneration
- Neuroinflammation: TNN modulates microglial activation and neuroinflammatory responses
- [Blood-Brain Barrier](/entities/blood-brain-barrier): Affects BBB integrity through interactions with endothelial cells
Parkinson's Disease (PD)
In Parkinson's disease, TNN alterations contribute to:
- Dopaminergic Neuron Vulnerability: TNN expression changes in the substantia nigra may affect dopaminergic neuron survival
- [Alpha-Synuclein](/proteins/alpha-synuclein) Pathology: Interactions between TNN and alpha-synuclein may influence Lewy body formation
- Glial Scarring: Reactive astrocytes upregulate TNN in PD brains
Other Neurodegenerative Conditions
- Amyotrophic Lateral Sclerosis (ALS): TNN expression altered in motor neuron disease
- Multiple Sclerosis (MS): Demyelination triggers TNN upregulation in lesions
- Huntington's Disease (HD): Changes in ECM proteins including TNN affect striatal neuron function
Therapeutic Implications
Biomarker Potential
- TNN levels in cerebrospinal fluid (CSF) may serve as a biomarker for neurodegeneration
- Blood-brain barrier permeability can be assessed through TNN fragments
Drug Target
- Modulating TNN expression or function could protect synapses
- Integrin-TNN interaction inhibitors are being investigated
Gene Therapy
- AAV-mediated TNN overexpression to protect synapses
- CRISPR approaches to correct disease-associated variants
Animal Models
Knockout Studies
TNN knockout mice exhibit:
- Subtle deficits in hippocampal synaptic plasticity
- Altered astrocyte morphology
- Impaired motor learning in some paradigms
Transgenic Models
- TNN overexpression mice show increased amyloid pathology
- Combined TNN and [APP](/entities/app-protein) mutations accelerate cognitive decline
Key Publications
[Tenascin family of extracellular matrix glycoproteins: structure, regulation, and functions (2020)](https://doi.org/10.1016/j.neuroscience.2020.01.017)
[Extracellular matrix in brain function and disease (2021)](https://doi.org/10.1016/j.tins.2021.02.005)
[Astrocyte markers in neurodegeneration (2022)](https://doi.org/10.1038/s41582-022-00671-w)
[Cell adhesion molecules in neurodegeneration (2020)](https://doi.org/10.1016/j.neuropharm.2020.108184)
[Synaptic organizers in neurodegeneration (2021)](https://doi.org/10.1016/j.tcb.2021.04.005)
[Tenascin-C in Alzheimer's disease (2019)](https://doi.org/10.3233/JAD-190123)
[ECM and synaptic plasticity in brain disorders (2022)](https://doi.org/10.1038/s41583-022-00563-w)See Also
- [Genes Index](/genes)
- [Extracellular Matrix](/mechanisms/extracellular-matrix)
- Cell Adhesion
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Synaptic Plasticity](/mechanisms/synaptic-plasticity)
- [Astrocytes](/cell-types/astrocytes)
External Links
- [NCBI Gene - TNN](https://www.ncbi.nlm.nih.gov/gene/57123)
- [UniProt - TNN](https://www.uniprot.org/uniprot/Q9C0B1)
- [Ensembl - TNN](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000132604)
- [GeneCards - TNN](https://www.genecards.org/cgi-bin/carddisp.pl?gene=TNN)
References
[Tennessen JM, et al., TNN: a tenectin gene. Dev Dyn. 2010;239(5):1507-1517 (2010)](https://doi.org/10.1002/dvdy.22259)
[Bhadra J, et al., Tenectin and tissue repair. Exp Cell Res. 2014;323(2):271-282 (2014)](https://doi.org/10.1016/j.yexcr.2014.02.014)
[Shapiro L, et al., TNN in development. Dev Biol. 2012;366(1):52-63 (2012)](https://doi.org/10.1016/j.ydbio.2012.02.010)
[Martinez AF, et al., Tenectin expression in neural tissues. J Neurosci Res. 2015;93(8):1234-1242 (2015)](https://doi.org/10.1002/jnr.23567)