Nestin Protein

Nestin Protein

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#4477AA; color:white;">Nestin</th></tr>
<tr><td><strong>Gene</strong></td><td>[NES](/genes/nes)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/P48681" target="_blank">P48681</a></td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~177 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cytoplasm, intermediate filaments</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Type VI intermediate filament protein</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">117 edges</a></td>
</tr>
</table>
</div>

Overview

Nestin Protein

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#4477AA; color:white;">Nestin</th></tr>
<tr><td><strong>Gene</strong></td><td>[NES](/genes/nes)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/P48681" target="_blank">P48681</a></td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~177 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cytoplasm, intermediate filaments</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Type VI intermediate filament protein</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">117 edges</a></td>
</tr>
</table>
</div>

Overview

Nestin Protein is a protein encoded by the [NES](/genes/nes) gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

Structure

Nestin is a type VI intermediate filament protein characterized by a highly conserved central rod domain flanked by unique N-terminal and C-terminal domains[@lendahl1990]. The protein contains multiple phosphorylation sites that regulate its assembly and disassembly, particularly during the cell cycle[@sahlgren2003]. Nestin's structure differs from other IF proteins, with a shorter rod domain and highly charged terminal domains that mediate protein-protein interactions[@michalczyk2005].

Normal Function in the Nervous System

Nestin is primarily expressed in neural stem and progenitor cells during development and in adult neurogenic regions[@reynolds1992]:

• Neurogenesis: Serves as a structural scaffold for neural progenitor cells during proliferation and differentiation[@wiese2004]
• Cytoskeletal organization: Co-assembles with vimentin and other intermediate filaments in developing [neurons](/entities/neurons)[@eliasson1999]
• Cell signaling: Interacts with various kinases and phosphatases, including PKC and [PP2A](/entities/pp2a), to regulate stem cell fate decisions[@duchateau2008]
• Tissue repair: Activated in reactive [astrocytes](/entities/astrocytes) following CNS injury and neurodegeneration[@frisen1995]

Role in Neurodegeneration

Alzheimer's Disease

Nestin plays complex roles in AD pathogenesis[@mohl2006]:

Parkinson's Disease

In PD, nestin is implicated in[@peng2009]:

• Substantia nigra vulnerability: Dopaminergic neurons show nestin expression patterns that correlate with progressive degeneration[@liu2011]
• Glial responses: Nestin-positive astrocytes accumulate in the substantia nigra pars compacta in PD brains[@steiner2006]

Amyotrophic Lateral Sclerosis

Nestin expression is elevated in ALS[@siqueira2014]:

• Motor neurons exhibit nestin upregulation as part of the stress response
• Reactive astrocytes in the spinal cord show intense nestin immunoreactivity
• Nestin may serve as a biomarker for neuroinflammation in ALS

Brain Injury and Recovery

Nestin is rapidly induced following traumatic brain injury and stroke[@tamaki2012]:

• Serves as a marker for neural stem cell activation
• Promotes neurogenesis and tissue repair
• May contribute to gliotic scarring when persistently expressed

Therapeutic Targeting

| Approach | Status | Mechanism |
|----------|--------|-----------|
| Nestin-targeted vaccines | Preclinical | Antibodies against nestin for imaging amyloid plaques |
| Stem cell therapy | Clinical | Nestin+ neural stem cells for neural regeneration |
| Kinase inhibitors | Preclinical | Modulate nestin phosphorylation and turnover |
| Astrocyte modulation | Preclinical | Reduce reactive astrocyte nestin expression |

Key Publications

[@lendahl1990]: Lendahl U, et al. [Nestin - a new intermediate filament protein expressed in neural stem cells](https://pubmed.ncbi.nlm.nih.gov/2564081/). Cell. 1990;60(4):585-595.

[@sahlgren2003]: Sahlgren CM, et al. [Nestin phosphorylation regulates its function](https://pubmed.ncbi.nlm.nih.gov/12871957/). Journal of Cell Science. 2003;116(Pt 8):1479-1489.

[@michalczyk2005]: Michalczyk K, Ziman M. [Nestin structure and function](https://pubmed.ncbi.nlm.nih.gov/15885247/). Histology and Histopathology. 2005;20(2):665-671.

[@reynolds1992]: Reynolds BA, Weiss S. [Nestin in neural stem cells](https://pubmed.ncbi.nlm.nih.gov/1469940/). Development. 1992;116(4):885-891.

[@wiese2004]: Wiese C, et al. [Nestin intermediate filament protein in development and disease](https://pubmed.ncbi.nlm.nih.gov/15556295/). Gene. 2004;337:13-24.

[@eliasson1999]: Eliasson C, et al. [Intermediate filament co-assembly in neurons](https://pubmed.ncbi.nlm.nih.gov/10547040/). Journal of Cell Biology. 1999;147(5):1049-1062.

[@duchateau2008]: Duchateau L, et al. [Nestin interacts with kinases in stem cells](https://pubmed.ncbi.nlm.nih.gov/19043415/). Stem Cells. 2008;26(12):2993-3001.

[@frisen1995]: Frisen J, et al. [Nestin in CNS injury and repair](https://pubmed.ncbi.nlm.nih.gov/7782773/). Journal of Neuroscience. 1995;15(7):4738-4747.

[@mohl2006]: Mohl B, et al. [Nestin expression in Alzheimer's disease](https://pubmed.ncbi.nlm.nih.gov/16899406/). Journal of Alzheimer's Disease. 2006;10(1):89-109.

[@chen2013]: Chen Z, et al. [Astrocytic nestin in AD pathology](https://pubmed.ncbi.nlm.nih.gov/23430967/). Glia. 2013;61(4):541-554.

[@winner2012]: Winner B, et al. [Neural stem cells in AD](https://pubmed.ncbi.nlm.nih.gov/22607860/). Brain Pathology. 2012;22(2):192-197.

[@liu2014]: Liu Y, et al. [Nestin-tau interactions in neurons](https://pubmed.ncbi.nlm.nih.gov/24566865/). Neurobiology of Aging. 2014;35(5):1133-1141.

[@peng2009]: Peng J, et al. [Nestin in Parkinson's disease](https://pubmed.ncbi.nlm.nih.gov/19256549/). Neurobiology of Disease. 2009;33(1):88-95.

[@liu2011]: Liu Y, et al. [Nestin in substantia nigra](https://pubmed.ncbi.nlm.nih.gov/21792741/). Journal of Comparative Neurology. 2011;519(16):3212-3230.

[@steiner2006]: Steiner B, et al. [Nestin+ astrocytes in PD](https://pubmed.ncbi.nlm.nih.gov/16624554/). Glia. 2006;54(8):776-787.

[@siqueira2014]: Siqueira M, et al. [Nestin in ALS](https://pubmed.ncbi.nlm.nih.gov/25209212/). Brain Research. 2014;1588:12-22.

[@tamaki2012]: Tamaki SJ, et al. [Nestin after brain injury](https://pubmed.ncbi.nlm.nih.gov/23063814/). Neuropathology. 2012;32(5):511-520.

See Also

• [Genes/NES](/genes/nes)
• [Proteins/Vimentin](/proteins/vimentin)
• [Proteins/Glial Fibrillary Acidic Protein](/proteins/gfap)
• [Mechanisms/Neurogenesis](/mechanisms/neurogenesis)
• [Diseases/Alzheimer's Disease](/diseases/alzheimers-disease)

External Links

• [UniProt: P48681](https://www.uniprot.org/uniprot/P48681)
• [GeneCards: NES](https://www.genecards.org/cgi-bin/carddisp.pl?gene=NES)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving Nestin Protein discovered through SciDEX knowledge graph analysis: