Nrf2-Activating Natural Compounds in Neurodegenerative Diseases: Targeting Oxidative Stress and Protein Aggregation

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Neurodegenerative diseases (NDs) are a major global health concern, characterized by complex mechanisms including oxidative stress, protein aggregation, and neuroinflammation.
• Current treatments for NDs are primarily symptomatic, lacking disease-modifying capabilities.
• Nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical transcription factor regulating cellular antioxidant and proteostasis pathways, and its dysregulation is implicated in ND pathogenesis.

Purpose of the Study:

• To review the role of oxidative stress and protein aggregation in major NDs such as Alzheimer's, Parkinson's, ALS, and Huntington's disease.
• To examine the neuroprotective potential of natural compounds derived from plants, fungi, and marine sources.
• To highlight the significance of Nrf2 activation as a mechanism underlying the therapeutic effects of these natural compounds.

Main Methods:

• Literature review focusing on oxidative stress, protein aggregation, and Nrf2 signaling in NDs.
• Analysis of studies investigating natural compounds for their effects on neuroprotection.
• Synthesis of information on the mechanisms of action, particularly Nrf2 activation and proteostasis maintenance.

Main Results:

• Natural bioactive compounds exhibit antioxidant, anti-aggregative, and anti-apoptotic properties relevant to NDs.
• Activation of Nrf2 signaling pathways is a common mechanism through which these compounds exert neuroprotection.
• Nrf2 plays a crucial role not only in redox regulation but also in maintaining proteostasis.

Conclusions:

• Nrf2-activating natural compounds represent promising multi-target agents for neuroprotection in NDs.
• These nutraceuticals can serve as valuable complementary strategies to conventional therapies.
• Targeting Nrf2 offers a potential avenue for developing disease-modifying treatments for neurodegenerative conditions.