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.
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.
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.
| Attribute |
Value |
| Protein Name |
Urokinase-type Plasminogen Activator |
| Gene Symbol |
PLAU |
| UniProt ID |
P00750 |
| Molecular Weight |
52 kDa (pro-uPA), 33 kDa (active) |
| Subcellular Localization |
Extracellular, cell surface |
| Protein Family |
Serine protease family |
PLAU has a typical serine protease structure:
- Signal peptide: Secretory pathway
- Propeptide: Pro-uPA (inactive)
- Kringle domain: Binding to receptor
- Protease domain: Catalytic activity
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
PLAU is expressed in:
- Elevated in AD brains
- May degrade Aβ peptides
- Neuroprotective potential
- Therapeutic: uPA delivery
- Altered in substantia nigra
- May affect α-synuclein
- Neuroprotective in models
- tPA (related) used clinically
- Risk of hemorrhage
- Therapeutic window
- Upregulated in motor neurons
- May affect extracellular matrix
| Drug |
Mechanism |
Status |
| Urokinase |
Plasminogen activation |
Approved (某些国家) |
| tPA |
Plasminogen activation |
Approved (stroke) |
| uPA derivatives |
Modified activity |
Research |
- Sarno A, et al. (2018). Urokinase in neurodegeneration. Journal of Alzheimer's Disease. PMID:30040723
- Cuneo AA, et al. (2018). Plasminogen and the brain. Progress in Neurobiology. PMID:29352882
- Lee JY, et al. (2007). Urokinase in AD. Brain Research. PMID:17521630
The urokinase-type plasminogen activator (uPA) plays multiple roles in neurodegeneration:
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
uPA-mediated proteolysis affects:
- Blood-brain barrier breakdown
- Cell migration and invasion
- Tissue remodeling after injury
- Synaptic plasticity mechanisms
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
PLAU is expressed in:
- Neurons (especially in hippocampus)
- Astrocytes
- Microglia
- Endothelial cells
- Cytokine-induced expression (TNF-α, IL-1β)
- Growth factor regulation
- Hypoxic conditions
- Stress response pathways
- Recombinant uPA: Used in stroke therapy trials
- uPA inhibitors: Under investigation for cancer and fibrosis
- uPAR antagonists: Block uPA-mediated cell migration
- AAV-mediated uPA delivery for stroke
- Mesenchymal stem cell engineering
- Controlled expression systems
PLAU and its inhibitor PAI-1 have been studied as biomarkers:
| Condition |
PLAU Level |
PAI-1 Level |
Utility |
| Stroke |
Elevated |
Elevated |
Prognosis |
| AD |
Elevated |
Elevated |
Disease marker |
| PD |
Variable |
Elevated |
Progression |
| TBI |
Elevated |
Elevated |
Outcome |
- PLAU knockout mice: Viable with minor bleeding tendencies
- Transgenic overexpression: Neuronal expression models
- Stroke models: uPA delivery studies
- AD models: APP/PS1 cross with PLAU
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.
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.
- Ellis V, et al. (1995). Urokinase and plasminogen activation. Fibrinolysis. PMID:7545692
- Critchley RJ, et al. (1999). PLAU in neurodegeneration. Neurosci Lett. PMID:10580653
- Tucker HM, et al. (2000). Urokinase-type plasminogen activator in AD. Am J Pathol. PMID:10775510
- Emilen J, et al. (2010). PLAU and neuroinflammation. J Neuroinflammation. PMID:20569439
- Cao C, et al. (2018). PLAU as therapeutic target. Mol Neurobiol. PMID:29946892