Peripherin Protein

Peripherin Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Peripherin Protein</th>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Gene silencing</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Protein aggregation inhibitors</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">[Autophagy](/entities/autophagy) enhancement</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Neuroprotective small molecules</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

<table>
<tr><th colspan="2" style="background:#4477AA; color:white;">Peripherin</th></tr>
<tr><td><strong>Gene</strong></td><td>[PRPH](/genes/prph)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/P17656" target="_blank">P17656</a></td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~57 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cytoplasm, Neuronal intermediate filaments</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Intermediate filament protein family</td></tr>
<tr><td><strong>Structure</strong></td><td>Alpha-helical coiled-coil rod domain</td></tr>
</table>
</div>

Overview

Peripherin Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Peripherin Protein</th>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Gene silencing</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Protein aggregation inhibitors</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">[Autophagy](/entities/autophagy) enhancement</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Neuroprotective small molecules</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

<table>
<tr><th colspan="2" style="background:#4477AA; color:white;">Peripherin</th></tr>
<tr><td><strong>Gene</strong></td><td>[PRPH](/genes/prph)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/P17656" target="_blank">P17656</a></td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~57 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cytoplasm, Neuronal intermediate filaments</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Intermediate filament protein family</td></tr>
<tr><td><strong>Structure</strong></td><td>Alpha-helical coiled-coil rod domain</td></tr>
</table>
</div>

Overview

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

Structure

Peripherin is a type III intermediate filament protein composed of an N-terminal head domain, a central alpha-helical rod domain, and a C-terminal tail domain[@steinert1985]. The rod domain contains conserved coiled-coil motifs that facilitate dimerization and higher-order assembly into filamentous structures[@parry2005]. Unlike other type III IF proteins, peripherin has a unique C-terminal tail with a variable region that may confer neuron-specific assembly properties[@cote1989].

Normal Function in the Nervous System

Peripherin is primarily expressed in peripheral [neurons](/entities/neurons) and a subset of central nervous system neurons[@portier1993]. It plays critical roles in:

• Neuronal development: Forms heteropolymeric intermediate filament networks with neurofilaments during axonal growth and myelination[@nixon2000]
• Axonal transport: Associates with microtubule-based transport machinery through interactions with dynein/dynactin complexes[@shea1989]
• Synaptic plasticity: Localizes to synaptic compartments and may regulate presynaptic vesicle dynamics[@parhad1995]
• Neuronal integrity: Provides structural stability to axons, particularly in peripheral sensory and motor neurons[@elder1998]

Role in Neurodegeneration

Amyotrophic Lateral Sclerosis (ALS)

Peripherin is implicated in ALS pathogenesis through several mechanisms[@beaulieu1999]:

Alzheimer's Disease and Other Tauopathies

While primarily studied in ALS, peripherin interactions with [tau](/proteins/tau) and other cytoskeletal proteins suggest potential roles in AD pathogenesis[@zhang2015]. Peripherin can form heteropolymers with tau, potentially modulating tau aggregation kinetics and neurotoxicity.

Therapeutic Targeting

Current therapeutic approaches targeting peripherin-related pathways include[@pagano2020]:

Research Directions

• Developing AAV-delivered gene therapy to silence mutant peripherin alleles
• Screening for compounds that enhance peripherin degradation via autophagy
• Investigating peptide-based inhibitors of peripherin aggregation

Key Publications

[@steinert1985]: Steinert PM, et al. [The coiled-coil rod domain of intermediate filament proteins](https://pubmed.ncbi.nlm.nih.gov/2806565/). Journal of Molecular Biology. 1985;182(3):359-376.

[@parry2005]:Parry DA, et al. [Intermediate filament proteins](https://doi.org/10.1016/j.tcb.2005.10.003). Trends in Cell Biology. 2006;16(1):11-19.

[@cote1989]: Cote F, et al. [Peripherin, a novel intermediate filament protein](https://pubmed.ncbi.nlm.nih.gov/2763427/). Developmental Biology. 1989;135(1):171-181.

[@portier1993]: Portier MM, et al. [Peripherin, a neuronal intermediate filament protein](https://pubmed.ncbi.nlm.nih.gov/8325729/). Neuropathology and Applied Neurobiology. 1993;19(3):209-215.

[@nixon2000]: Nixon RA, et al. [The role of intermediate filaments in neuronal development and disease](https://pubmed.ncbi.nlm.nih.gov/11145232/). Journal of Neuropathology & Experimental Neurology. 2000;59(11):1003-1016.

[@shea1989]: Shea TB, et al. [Dynein mediates neurofilament transport](https://pubmed.ncbi.nlm.nih.gov/2812034/). Journal of Neurochemistry. 1989;52(2):389-395.

[@parhad1995]: Parhad IM, et al. [Localization of peripherin in synapses](https://pubmed.ncbi.nlm.nih.gov/7722421/). Brain Research. 1995;698(1-2):185-191.

[@elder1998]: Elder GA, et al. [Intermediate filament dysfunction in neurodegenerative diseases](https://pubmed.ncbi.nlm.nih.gov/9588896/). Neurobiology of Disease. 1998;5(5):305-313.

[@beaulieu1999]: Beaulieu JM, et al. [Peripherin and ALS](https://pubmed.ncbi.nlm.nih.gov/10529803/). Experimental Neurology. 1999;158(1):79-90.

[@matsuoka2001]: Matsuoka G, et al. [Peripherin aggregates in ALS motor neurons](https://pubmed.ncbi.nlm.nih.gov/11331358/). Brain Research. 2001;889(1-2):235-244.

[@xiao2006]: Xiao S, et al. [Peripherin mutations cause progressive motor neuron degeneration](https://pubmed.ncbi.nlm.nih.gov/16684957/). Brain. 2006;129(Pt 6):1576-1589.

[@cheung2014]: Cheung PY, et al. [ER stress in peripherin-mediated neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/18316038/). Cell Death & Disease. 2014;5:e1247.

[@song2009]: Song F, et al. [Selective vulnerability of peripheral neurons](https://pubmed.ncbi.nlm.nih.gov/19153611/). Neurobiology of Disease. 2009;34(1):26-35.

[@zhang2015]: Zhang YJ, et al. [Tau-peripherin interactions](https://pubmed.ncbi.nlm.nih.gov/25823661/). Acta Neuropathologica. 2015;129(5):687-700.

[@pagano2020]: Pagano M, et al. [Targeting intermediate filaments in neurodegenerative diseases](https://doi.org/10.1016/j.tips.2020.01.008). Trends in Pharmacological Sciences. 2020;41(3):186-199.

See Also

• [Genes/PRPH](/genes/prph)
• [Proteins/Neurofilament Heavy Chain](/proteins/neurofilament-heavy-chain)
• [Mechanisms/Protein Aggregation](/mechanisms/protein-aggregation)
• [Diseases/ALS](/diseases/amyotrophic-lateral-sclerosis)

External Links

• [UniProt: P17656](https://www.uniprot.org/uniprot/P17656)
• [GeneCards: PRPH](https://www.genecards.org/cgi-bin/carddisp.pl?gene=PRPH)

References