Creating a SlideShare presentation on the NF-kB signaling pathway is a great way to share information about this important cellular process. Here's a brief outline and description of key points you can include in your presentation: Slide 1: Title - Title: "NF-kB Signaling Pathway: Unveiling Cellular Regulation" Slide 2: Introduction - Introduction to NF-kB: Explain that NF-kB (Nuclear Factor-kappa B) is a crucial transcription factor involved in regulating gene expression and plays a pivotal role in immune responses, inflammation, and cell survival. Slide 3: Structure of NF-kB - Describe the structure of NF-kB, including its different subunits and how they combine to form active NF-kB dimers. Slide 4: Signaling Pathway Overview - Provide an overview of the NF-kB signaling pathway, emphasizing that it is activated in response to various stimuli, such as cytokines, pathogens, and stress. Slide 5: Activation of NF-kB - Explain how NF-kB is activated, including the role of IkappaB (Inhibitor of kappa B) proteins and the phosphorylation and degradation process. Slide 6: NF-kB Targets - Discuss the types of genes that NF-kB regulates, including those involved in inflammation, cell survival, and immune responses. Slide 7: Regulation of NF-kB - Describe the mechanisms that control NF-kB activity, such as negative feedback loops and other regulatory proteins. Slide 8: NF-kB in Diseases - Highlight the significance of NF-kB in various diseases, such as cancer, autoimmune disorders, and chronic inflammation. Slide 9: Therapeutic Implications - Discuss how targeting the NF-kB pathway has therapeutic implications and potential treatments for NF-kB-related diseases. Slide 10: Conclusion - Summarize the key points discussed in the presentation and emphasize the importance of understanding NF-kB signaling in cellular processes and disease. Slide 11: Questions and Discussion - Open the floor for questions and discussions from your audience. Slide 12: References - List the sources and references used in your presentation. Ensure that your slides are visually engaging with relevant images, diagrams, and concise text. This structure will help your audience understand the NF-kB signaling pathway and its significance in cellular regulation and disease.

1. Nf-kB signaling
Pathway

2. INTRODUCTION

3. INTRODUCTION
The NF kB stands for:
Nuclear factor kappa-light-chain-enhancer of activated B cells.
It is a highly conserved and complex signaling pathway that is
involved in regulating variety of cellular processes including
• Inflammation
• Immunity
• Cell growth
• Cell survival

4. Role of Nf-kB in immunity:
• NF-kB regulates both innate and adaptive immune
responses. It is activated rapidly in response to a wide range
of stimuli, including pathogens, stress signals and pro-
inflammatory cytokines, such as tumor-necrosis factor (TNF)
and interleukin-1 (IL-1)

5. Role of Nf-kB pathway in
lymphocytes development
• NF-kB has important functions in shaping the immune system
so it is able to generate adaptive responses to pathogens. In
both contexts, NF-kB executes critical cell-autonomous
functions within lymphocytes as well as within supportive
cells, such as antigen-presenting cells or epithelial cells.

6. Ligand
Receptor
Secondary
messengers
Transcription factors
Cellular effect
1
2 4
3
5
DNA Transcription,
cytokine production
NF-kB
IK,IIKB,NFKB,NIK
TNFR,TLR
TNF, cytokines, IL-1
1
2 4
5 fingers to remember NF kB cell signaling

7. • Presented by: Iqra Iftikhar
• Reg No: 100-FBAS/BSBIO/lF19
Canonical signaling refers to a specific pathway of
signal transduction that is well-defined and widely
accepted.
Canonical signaling
pathway

8. Canonical NF-kB pathway
• The IκBα(inhibitor of nuclear factor kappa B) protein inactivates the
NF-κB transcription factor by masking the nuclear
localization signals (NLS) of NF-κB proteins, keeping
them in an inactive state in the cytoplasm
Inactive

9. NUCLEUS
Cytoplasm
Proteasome
Inactive Nf-kB(dimer)
No ligand
Inactive
p50
Rel a
IkBα

10. Canonical NF-kB pathway
• IKK (IkappaB kinase or IKK) phosphorylates the inhibitory IκBα
protein.
• This phosphorylation results in the dissociation of IκBα
from NF-κB.
• NF-κB, which is now free, migrates into the nucleus and
activates the expression of at least 150 genes; some of
which are anti-apoptotic.
active

11. Inactive Nf-kB(dimer)
p50
Rel A
IkBα
NUCLEUS
Cytoplasm
ligand
IKKα
p50
Rel A
IkBα
p p
Co-
activators
IkBα
p p
p50
Rel A
Proteasome
p50
Rel A
active Nf-kB(dimer)
active

12. Non-Canonical signaling
pathway

13. Non canonical NF kB pathway
• An imp arm of NF kB signaling that targets activation of p52/ ReIb
NF kB complex.
Canonical vs non canonical NF kB signaling:
• Different cell receptors and ligands,
• IKKα instead of IKKβ,
• Slow activation compared to canonical (hours).

14. NIK
TRAF3
TRAF2
CIAP1/2
UB
UB
UB
Proteasome
p100 ReIb
Inactive dimer
BAFF, LTβ
Inactive state:

15. TRAF3
TRAF2
CIAP1/2
BAFF, LTƅ ACTIVATED
NIK
IKKα
P
p100 ReIb Inactive dimer
P
UB
UB
UB
p52 ReIb
Active dimer
p52

16. Dysregulation of NF-KB

17. Causes:
The NF-kB pathway can become dysregulated due to
various factors including:
• Genetic mutations
• Dysregulation of upstream signaling pathways
• Environmental stressors
• Viral infections

18. Pathological Consequences
Dysregulation of the NF-kB pathway has been implicated in
various pathological conditions, including
1- Cancer:
Aberrant activation of the NF-kB pathway has been linked to the
development and progression of various types of cancer, by excessive innate
immunity activation and abnormal cell growth.
2-Autoimmune disorders:
Dysregulation of the NF-kB pathway can lead to the development of
autoimmune disorders by mediating the activation and differentiation of
autoimmune and inflammatory T cells, such as Th17 cells.

19. 3- Inflammatory diseases:
The NF-kB pathway is a key regulator of inflammation, and its
dysregulation has been implicated in various inflammatory diseases by
increasing the production of inflammatory cytokines, chemokines and
adhesion molecules.
4-Infectious diseases:
Some pathogens, such as viruses and bacteria, have developed
mechanisms to hijack the NF-kB pathway to evade immune
detection and promote their own survival. This can lead to chronic
infections and persistent inflammation.

20. Therapeutic implications

21. • The nuclear factor-kappa B (NF-κB) signaling pathway
regulates various cellular processes
• Dysregulation of NF-κB signaling pathological conditions,
Inflammation survival
cell
proliferation
Immune
response
chronic
inflammatory
disorders
Autoimmune diseases
Cancer

22. 1. Anti-inflammatory effects
• Making it an attractive target for the treatment of inflammatory diseases such
as rheumatoid arthritis, inflammatory bowel disease, and asthma.
Drug sulfasalazine
Inhibits NF-κB signalling
Used to treat inflammatory bowel disease.

23. • Dysregulation of NF-κB signaling has been implicated in the pathogenesis of
neurodegenerative diseases such as Alzheimer's and Parkinson's disease.
• NF-κB signaling is frequently activated in cancer cells, promoting tumor
growth, invasion, and metastasis.
• Targeting this pathway has been explored as a potential cancer therapy.
• Several drugs that inhibit NF-κB signaling,
Used for the treatment of multiple myeloma and other types of cancer.
Thalidomide
2. Cancer Therapy

24. Conclusion
• More research is needed to develop selective and effective drugs that can target this pathway
without causing unwanted side effects.
• Complete inhibition of this pathway may have unwanted side effects.
• Targeting this pathway needs to be done in a selective and precise manner, to avoid disrupting
normal cellular functions.