PLAU Protein

PLAU Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">PLAU Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Urokinase-type Plasminogen Activator</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PLAU</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P00750</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>52 kDa (pro-uPA), 33 kDa (active)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Extracellular, cell surface</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Serine protease family</td>
</tr>
<tr>
<td class="label">Drug</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Urokinase</td>
<td>Plasminogen activation</td>
</tr>
<tr>
<td class="label">tPA</td>
<td>Plasminogen activation</td>
</tr>
<tr>
<td class="label">uPA derivatives</td>
<td>Modified activity</td>
</tr>
<tr>
<td class="label">Condition</td>
<td>PLAU Level</td>
</tr>
<tr>
<td class="label">Stroke</td>
<td>Elevated</td>
</tr>
<tr>
<td class="label">AD</td>
<td>Elevated</td>
</tr>
<tr>
<td class="label">PD</td>
<td>Variable</td>
</tr>
<tr>
<td class="label">TBI</td>
<td>Elevated</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">A

...

PLAU Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">PLAU Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Urokinase-type Plasminogen Activator</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PLAU</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P00750</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>52 kDa (pro-uPA), 33 kDa (active)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Extracellular, cell surface</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Serine protease family</td>
</tr>
<tr>
<td class="label">Drug</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Urokinase</td>
<td>Plasminogen activation</td>
</tr>
<tr>
<td class="label">tPA</td>
<td>Plasminogen activation</td>
</tr>
<tr>
<td class="label">uPA derivatives</td>
<td>Modified activity</td>
</tr>
<tr>
<td class="label">Condition</td>
<td>PLAU Level</td>
</tr>
<tr>
<td class="label">Stroke</td>
<td>Elevated</td>
</tr>
<tr>
<td class="label">AD</td>
<td>Elevated</td>
</tr>
<tr>
<td class="label">PD</td>
<td>Variable</td>
</tr>
<tr>
<td class="label">TBI</td>
<td>Elevated</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">77 edges</a></td>
</tr>
</table>

Overview

Plau Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Introduction

Plau Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. [@critchley1999]

The PLAU protein (Plasminogen Activator, Urokinase), also known as urokinase-type plasminogen activator (uPA), is a serine protease that converts plasminogen to plasmin. It has roles in fibrinolysis, extracellular proteolysis, and cell migration. [@tucker2000]

Protein Overview

Structure

PLAU has a typical serine protease structure:

• Signal peptide: Secretory pathway
• Propeptide: Pro-uPA (inactive)
• Kringle domain: Binding to receptor
• Protease domain: Catalytic activity

Normal Function

Urokinase is a key fibrinolytic enzyme:

• Plasmin generation: Converts plasminogen to plasmin
• Fibrinolysis: Dissolves blood clots
• ECM degradation: Activates metalloproteinases
• Cell migration: Facilitates tissue remodeling

Expression in Brain

PLAU is expressed in:

• [Neurons](/entities/neurons)
• [Astrocytes](/entities/astrocytes)
• [Microglia](/entities/microglia)
• Endothelial cells

Role in Disease

Alzheimer's Disease

• Elevated in AD brains
• May degrade [Aβ](/proteins/amyloid-beta) peptides
• Neuroprotective potential
• Therapeutic: uPA delivery

Parkinson's Disease

• Altered in substantia nigra
• May affect [α-synuclein](/proteins/alpha-synuclein)
• Neuroprotective in models

Stroke

• tPA (related) used clinically
• Risk of hemorrhage
• Therapeutic window

ALS

• Upregulated in motor neurons
• May affect extracellular matrix

Therapeutic Targeting

Key Publications

• Sarno A, et al. (2018). Urokinase in neurodegeneration. Journal of Alzheimer's Disease. PMID: 30040723(https://pubmed.ncbi.nlm.nih.gov/30040723/)
• Cuneo AA, et al. (2018). Plasminogen and the brain. Progress in Neurobiology. PMID: 29352882(https://pubmed.ncbi.nlm.nih.gov/29352882/)
• Lee JY, et al. (2007). Urokinase in AD. Brain Research. PMID: 17521630(https://pubmed.ncbi.nlm.nih.gov/17521630/)

See Also

• [PLAU Gene](/proteins/plau-protein)
• [Fibrinolysis Pathway](/mechanisms/fibrinolysis)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Stroke](/diseases/stroke)

External Links

• [UniProt: PLAU](https://www.uniprot.org/uniprot/P00750)
• [PDB: 1GJA](https://www.ebi.ac.uk/pdbe/entry/pdb/1GJA)
• [GeneCards: PLAU](https://www.genecards.org/cgi-bin/carddisp.pl?gene=PLAU)

Molecular Mechanisms

The urokinase-type plasminogen activator (uPA) plays multiple roles in neurodegeneration:

Plasminogen Activation Cascade

PLAU catalyzes the conversion of plasminogen to plasmin:

• Plasmin is a broad-spectrum protease
• Activates other proteases (MMPs)
• Degrades fibrin and extracellular matrix
• Processes growth factors and cytokines

Extracellular Proteolysis

uPA-mediated proteolysis affects:

• [Blood-brain barrier](/entities/blood-brain-barrier) breakdown
• Cell migration and invasion
• Tissue remodeling after injury
• Synaptic plasticity mechanisms

Cell Surface Signaling

uPA binds to the uPA receptor (uPAR):

• Promotes cell adhesion and migration
• Activates intracellular signaling pathways
• Modulates integrin function
• Influences immune cell trafficking

Expression and Regulation

Brain Expression

PLAU is expressed in:

• Neurons (especially in hippocampus)
• [Astrocytes](/cell-types/astrocytes) [Microglia](/cell-types/microglia-neuroinflammation)
• Endothelial cells

Regulatory Mechanisms

• Cytokine-induced expression (TNF-α, IL-1β)
• Growth factor regulation
• Hypoxic conditions
• Stress response pathways

Therapeutic Approaches

uPA Modulators

• Recombinant uPA: Used in stroke therapy trials
• uPA inhibitors: Under investigation for cancer and fibrosis
• uPAR antagonists: Block uPA-mediated cell migration

Gene Therapy

• AAV-mediated uPA delivery for stroke
• Mesenchymal stem cell engineering
• Controlled expression systems

Biomarker Potential

PLAU and its inhibitor PAI-1 have been studied as biomarkers:

Research Models

• PLAU knockout mice: Viable with minor bleeding tendencies
• Transgenic overexpression: Neuronal expression models
• Stroke models: uPA delivery studies
• AD models: [APP](/entities/app-protein)/PS1 cross with PLAU

Overview

Plau Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Background

The study of Plau Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

[Ellis V, et al. (1995), Urokinase and plasminogen activation (1995)](https://pubmed.ncbi.nlm.nih.gov/7545692/)

[Critchley RJ, et al. (1999), PLAU in neurodegeneration (1999)](https://pubmed.ncbi.nlm.nih.gov/10580653/)

[Tucker HM, et al. (2000), Urokinase-type plasminogen activator in AD (2000)](https://pubmed.ncbi.nlm.nih.gov/10775510/)

[Emilen J, et al. (2010), PLAU and neuroinflammation (2010)](https://pubmed.ncbi.nlm.nih.gov/20569439/)

[Cao C, et al. (2018), PLAU as therapeutic target (2018)](https://pubmed.ncbi.nlm.nih.gov/29946892/)