Nestin Protein

📖 Wiki Page

protein906 wordssynced 2026-04-02

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

Overview

Mermaid diagram (expand to render)

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]:

Astrocytic reactivation: Nestin is upregulated in reactive astrocytes surrounding amyloid plaques and neurofibrillary tangles, serving as a marker of neuroinflammation[@chen2013]

Stem cell response: Neural stem cells in the subventricular zone show increased nestin expression in AD, representing endogenous repair attempts[@winner2012]

[Tau](/proteins/tau) pathology: Nestin co-localizes with phosphorylated tau in neurons, potentially participating in cytoskeletal disruption[@liu2014]

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.

External Links

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

References

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

[Sahlgren CM, et al, Nestin phosphorylation regulates its function (2003)](https://pubmed.ncbi.nlm.nih.gov/12871957/)

[Michalczyk K, Ziman M, Nestin structure and function (2005)](https://pubmed.ncbi.nlm.nih.gov/15885247/)

[Reynolds BA, Weiss S, Nestin in neural stem cells (1992)](https://pubmed.ncbi.nlm.nih.gov/1469940/)

[Wiese C, et al, Nestin intermediate filament protein in development and disease (2004)](https://pubmed.ncbi.nlm.nih.gov/15556295/)

[Eliasson C, et al, Intermediate filament co-assembly in neurons (1999)](https://pubmed.ncbi.nlm.nih.gov/10547040/)

[Duchateau L, et al, Nestin interacts with kinases in stem cells (2008)](https://pubmed.ncbi.nlm.nih.gov/19043415/)

[Frisen J, et al, Nestin in CNS injury and repair (1995)](https://pubmed.ncbi.nlm.nih.gov/7782773/)

[Mohl B, et al, Nestin expression in Alzheimer's disease (2006)](https://pubmed.ncbi.nlm.nih.gov/16899406/)

[Chen Z, et al, Astrocytic nestin in AD pathology (2013)](https://pubmed.ncbi.nlm.nih.gov/23430967/)

[Winner B, et al, Neural stem cells in AD (2012)](https://pubmed.ncbi.nlm.nih.gov/22607860/)

[Liu Y, et al, Nestin-tau interactions in neurons (2014)](https://pubmed.ncbi.nlm.nih.gov/24566865/)

[Peng J, et al, Nestin in Parkinson's disease (2009)](https://pubmed.ncbi.nlm.nih.gov/19256549/)

[Liu Y, et al, Nestin in substantia nigra (2011)](https://pubmed.ncbi.nlm.nih.gov/21792741/)

[Steiner B, et al, Nestin+ astrocytes in PD (2006)](https://pubmed.ncbi.nlm.nih.gov/16624554/)

[Siqueira M, et al, Nestin in ALS (2014)](https://pubmed.ncbi.nlm.nih.gov/25209212/)

[Tamaki SJ, et al, Nestin after brain injury (2012)](https://pubmed.ncbi.nlm.nih.gov/23063814/)

Pathway Diagram

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

Mermaid diagram (expand to render)

📖 View canonical wiki page →

Nestin Protein

Nestin Protein

Overview

Nestin Protein

Overview

Structure

Normal Function in the Nervous System

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Brain Injury and Recovery

Therapeutic Targeting

Key Publications

See Also

External Links

References

Pathway Diagram