NF-κB (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells) Pathway

The NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway is a critical cellular signaling pathway that regulates inflammation, immune response, cell survival, and gene expression in response to stress or pathogens.

🧬 What Is the NF-κB Pathway?

It’s a protein complex that acts as a transcription factor — meaning it controls which genes are turned on or off in response to stimuli like:

Infection
Inflammatory cytokines
Free radicals (oxidative stress)
UV radiation
Tissue injury

🔄 How It Works (Simplified):

In the resting state, NF-κB is bound to an inhibitor protein called IκB and held in the cytoplasm (outside the nucleus).
When a signal comes in (e.g., infection or stress), an enzyme complex called IKK phosphorylates IκB.
IκB is destroyed, which frees NF-κB to move into the nucleus.
Once in the nucleus, NF-κB binds to DNA and activates genes involved in:
- Inflammation
- Immune defense
- Cell proliferation
- Survival (anti-apoptosis)

🔥 Key Functions of the NF-κB Pathway:

Function	Examples
Immune response	Activates cytokines like TNF-α, IL-1, IL-6
Inflammation	Drives inflammatory gene expression
Cell survival	Promotes anti-apoptotic proteins (helps cancer cells survive)
Stress response	Activated by oxidative stress, radiation, infections
Autoimmunity / Allergy	Overactivation linked to autoimmune conditions, chronic inflammation

⚠️ When NF-κB Becomes a Problem:

Chronic or excessive activation of NF-κB is linked to:

Chronic inflammatory diseases (e.g., rheumatoid arthritis, IBD)
Cancer (helps tumor cells resist death)
Neurodegenerative diseases (e.g., Alzheimer’s)
Metabolic disorders (e.g., insulin resistance)

💊 Therapeutic Target

Drugs and natural compounds that inhibit NF-κB are being studied or used to reduce inflammation:
- Curcumin (turmeric)
- Resveratrol
- Aspirin & NSAIDs
- Corticosteroids
- Targeted biologics in autoimmune disease

🧠 In Summary:

The NF-κB pathway is a central switch for inflammation and immune defense. It’s essential for survival during infection or injury — but when overactive, it contributes to chronic disease, aging, and cancer.