PLAU Protein

📖 Wiki Page

protein834 wordssynced 2026-04-02

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

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/)

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

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/)

📖 View canonical wiki page →

PLAU Protein

PLAU Protein

PLAU Protein

Overview

Introduction

Protein Overview

Structure

Normal Function

Expression in Brain

Role in Disease

Alzheimer's Disease

Parkinson's Disease

Stroke

ALS

Therapeutic Targeting

Key Publications

See Also

External Links

Molecular Mechanisms

Plasminogen Activation Cascade

Extracellular Proteolysis

Cell Surface Signaling

Expression and Regulation

Brain Expression

Regulatory Mechanisms

Therapeutic Approaches

uPA Modulators

Gene Therapy

Biomarker Potential

Research Models

Overview

Background

References