Toll like receptor (TLR) and nucleotide-binding oligomerization domain (NOD), leucine-rich repeat (LRR)-containing proteins (NLR) proteins form sensors on our immune cells to detect pathogen associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs). TLR receptors when activated prime the NLRP3 receptors. NLRP3 receptors when activated trigger the production of inflammasomes and subsequent cell death by pyroptosis. Both of these receptors and their pathways are important in creation and maintenance of inflammation. However, in subclinical/chronic inflammation these pathways can become potentially dysregulated. In this talk we will present an overview of these pathways, their interaction with each other and the possible ways to modulate these pathways.

Objectives:

1. Quick review of the key inflammatory pathways.

2. TLR pathway overview. 3. How TLR pathway primes NLRP

3.  Pathway.

4. NLRP3 pathway and its function for inflammasomal activity.

5. What are inflammasomes?

6. Studies demonstrating micronutrients that can modulate these pathways.

7. Role of hydroxychloroquine while modulating these pathways.

TLR Pathway Modulators Vitamin D, B12, A, Zinc, Copper, and Iron, Microbiome

Micronutrients and many important factors that affect the physiological functions of toll-like receptors | Bulletin of the National Research Centre | Full Text https://bnrc.springeropen.com/articles/10.1186/s42269-019-0165-z

The Association Between Gut Microbiota, Toll-Like Receptors, and Colorectal Cancer - PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9634190/

The TLR signaling pathway and downstream effector molecules. Depicted... | Download Scientific Diagram https://www.researchgate.net/figure/The-TLR-signaling-pathway-and-downstream-effector-molecules-Depicted-are-key-TLR_fig1_47567186

Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study | Signal Transduction and Targeted Therapy https://www.nature.com/articles/s41392-020-00312-6

NLRP Pathway Modulators Important molecules involved in this pathway: Caspase-1, Caspase-11, cleavage of pro-IL-1beta and pro-IL-18 to IL-1beta and IL-18 (central to inflammation), Gasdermin D activation (creating membrane pores for pryoptosis (fiery death.)

We need to modulate NLRP pathway towards autophagic pathway and away from pyroptotoic pathway. Substances below help do it. However, don't use hydroxychloroquine with these to modulate NLRP, because HCQ will block autophagy and hence the effect of these supplements.

Note: in case you feel that the pyroptosis and autophagy both need to be stopped then HCQ can be used in combination with the products below.

Interventions:

Vitamin D, Omega-3, Curcumin, Resveratrol, Diet, and Exercise

The role of vitamin D3 in modulating the interplay between NLRP3 inflammasome and autophagy in NASH - PubMed https://pubmed.ncbi.nlm.nih.gov/37951152/

The role of vitamin D3 in modulating the interplay between NLRP3 inflammasome and autophagy in NASH - PubMed https://pubmed.ncbi.nlm.nih.gov/37951152/

Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance - PubMed https://pubmed.ncbi.nlm.nih.gov/25149823/

The Effects of Curcumin on Inflammasome: Latest Update - PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866118/

Resveratrol inhibits NLRP3 inflammasome activation by preserving mitochondrial integrity and augmenting autophagy - PubMed https://pubmed.ncbi.nlm.nih.gov/25535911/

The Effect of Adherence to Mediterranean Diet on Disease Activity in Patients with Inflammatory Bowel Disease - PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10441165/

The anti-inflammatory effect of exercise | Journal of Applied Physiology https://journals.physiology.org/doi/full/10.1152/japplphysiol.00164.2004

Allopathic Medicine: No drugs at the moment that modulate NLRP. However, there are molecules in pre-clinical and clinical trials to modulate NLRP.

Allopathic Medicine: No drugs at the moment that modulate NLRP. However, there are molecules in pre-clinical and clinical trials to modulate NLRP.