Cytoprotective protein C pathways and implications for stroke and neurological disorders

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Berislav V Zlokovic1, John H Griffin

  • 1Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurological Surgery, University of Rochester Medical Center, Rochester, New York, USA. berislav_zlokovic@urmc.rochester.edu

Trends in Neurosciences
|March 1, 2011
PubMed

Insights

Activated protein C (APC), a protease, shows promise for treating CNS disorders by targeting vascular damage, neuronal injury, and neuroinflammation. Its multi-action approach offers potential disease-modifying therapies for conditions like ischemic stroke.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Vascular Biology

Background:

  • Central nervous system (CNS) disorders often involve a triad of vascular damage, neuronal injury/neurodegeneration, and neuroinflammation.
  • Single-action agents are insufficient for treating complex CNS pathologies.

Purpose of the Study:

  • To explore the potential of activated protein C (APC) as a multiple-action-multiple-target therapeutic for CNS disorders.
  • To investigate APC's biological properties and signaling pathways in the context of neurovascular and inflammatory processes.

Main Methods:

  • Focus on newly discovered biological properties of activated protein C (APC).
  • Examined APC-mediated signaling through protease-activated receptor-1 (PAR1).
  • Evaluated effects on the neurovascular unit in preclinical models of CNS insults.

Main Results:

  • APC exhibits antithrombotic, cytoprotective, and anti-inflammatory activities in the CNS.
  • APC signaling via PAR1 favorably regulates pathways in the neurovascular unit.
  • Demonstrated potential for blood-brain barrier (BBB) stabilization, neuroprotection, and control of neuroinflammation.

Conclusions:

  • Activated protein C (APC) presents a promising disease-modifying therapeutic strategy for CNS disorders.
  • APC's multi-target approach addresses the vascular, neuronal, and inflammatory components of neuropathologies.
  • Further research into APC biology is warranted for its application in conditions like ischemic stroke.

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