Peroxiredoxins in Stroke: Friends and Foes

Area of Science:

• Neuroscience
• Biochemistry
• Pathology

Background:

• Stroke causes significant mortality and disability via oxidative stress and neuroinflammation.
• The peroxiredoxin (Prx) family, comprising six thiol-dependent antioxidant enzymes (Prx1-6), is vital for redox homeostasis and brain immune responses.

Purpose of the Study:

• To review the specific roles of Prx isoforms in ischemic and hemorrhagic stroke.
• To highlight the dual and context-dependent functions of Prxs in stroke pathophysiology.
• To explore the potential of Prxs as diagnostic biomarkers and therapeutic targets for stroke.

Main Methods:

• Literature review synthesizing current knowledge on Prx isoforms in stroke.
• Analysis of Prx functions in neuronal protection, blood-brain barrier integrity, inflammation, and mitochondrial/endothelial effects.
• Discussion of emerging research tools and translational potential.

Main Results:

• Intracellular Prxs generally offer neuroprotection and maintain blood-brain barrier (BBB) integrity.
• Extracellular Prx1 and Prx2 act as damage-associated molecular patterns (DAMPs), promoting inflammation via toll-like receptor signaling.
• Prx3 and Prx4 show mitochondrial and endothelial protective effects, respectively; Prx6 has complex roles influenced by its aiPLA2 activity and localization.

Conclusions:

• Prx isoforms exhibit diverse, context-dependent roles in stroke, acting as both protective and detrimental factors.
• Understanding Prx dynamics is key to developing novel diagnostic and therapeutic strategies for stroke.
• Prxs represent promising targets for future stroke interventions and biomarker development.