The Nrf2 pathway in psychiatric disorders: pathophysiological role and potential targeting

Area of Science:

• Neuroscience
• Psychiatry
• Molecular Biology

Background:

• Psychiatric disorders share common pathologies including excitotoxicity, mitochondrial dysfunction, inflammation, oxidative stress, and neural damage.
• The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is a critical endogenous defense mechanism against oxidative stress.
• Nrf2 signaling is significantly implicated in the pathophysiology of various psychiatric disorders.

Purpose of the Study:

• To explore the role of the Nrf2 pathway and its modulators in psychiatric disorders.
• To review the current literature on Nrf2's involvement in the biological underpinnings of mental health conditions.

Main Methods:

• Comprehensive literature search conducted across major scientific databases (Embase, Medline, Web of Science, PubMed, Google Scholar) from 2010 to 2020.
• Inclusion of diverse study types: research articles, clinical reports, systematic reviews, and meta-analyses.
• Focus on studies investigating Nrf2 pathway activity and therapeutic modulation in psychiatric contexts.

Main Results:

• Nrf2 plays a dual role by downregulating inflammatory pathways and upregulating antioxidant enzymes, crucial for maintaining cellular balance.
• The balance between Nrf2 and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ) is critical during severe oxidative stress.
• Several Nrf2 modulators are currently undergoing clinical trials for their potential to mitigate oxidative stress and neuroinflammation.

Conclusions:

• Nrf2 pathway dysregulation is a significant factor in psychiatric disorders.
• Nrf2 modulators represent a promising avenue for novel therapeutic strategies in psychiatry.
• Targeting Nrf2 offers potential for reducing neuroinflammation and oxidative stress, improving treatment outcomes.