TNN Gene

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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

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

Extracellular Matrix Organization

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 synapses

Axon 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)

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)

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TNN Gene

TNN Gene

Gene Overview

Background

TNN Gene

Gene Overview

Background

Expression Pattern

Brain Regions

Cellular Expression

Normal Function

Extracellular Matrix Organization

Synaptic Function

Axon Guidance

Glial-Neuronal Interactions

Disease Associations

Alzheimer's Disease (AD)

Parkinson's Disease (PD)

Other Neurodegenerative Conditions

Therapeutic Implications

Biomarker Potential

Drug Target

Gene Therapy

Animal Models

Knockout Studies

Transgenic Models

Key Publications

See Also

External Links

References