Targeting NLRP3

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Targeting-NLRP3According to the World health Organization noncommunicable diseases (NCDs), otherwise known as chronic diseases, are responsible for 71% of deaths globally, this shift away from death as a result of infectious diseases has occurred in most industrialised nations over the last century. Most NCDs occur later in life and are the result of a combination of genetic, physiological, environmental and behaviour factors.


Our immune cells play a key role in maintaining tissue stability, which is vital for our organs to function correctly. Immune cells have an array of germline-encoded signal receptors and so can gather information detecting and responding to infection, tissue damage or metabolic derangements. One of these receptors, the NLRP3 inflammasome, mediates the activation of potent inflammatory mediators and is key to the origination and science is beginning to qualify how it may be significantly involved in the development of many NCDs.


NLRP3 activation is linked to a range of triggers including mitochondrial dysfunction, with mitochondrial reactive oxygen species (mtROS) being essential for NLRP3 triggering which in turn goes on to increase production of mtROS. NLRP3 activation via oxidative stress can be inhibited by preincubation with some antioxidants and suggests that nutritional intake may be able to mediate the inappropriate activation of this defence mechanism. The origin and development of many common diseases are influenced by the presence of sterile danger signals in tissues (alarmins), of which NLRP3 is the primary sensor. NLRP3 is a contributor in genetic NLRP3-dependant auto-inflammatory diseases, diseases driven by metabolic dysfunction, diseases caused by the formation of crystals or aggregates, and fibrosis following acute tissue injury or chronic inflammation. These include #Alzheimer’s, #MultipleSclerosis, #Strokes #Diabetes and #Arthritis.


These metabolic diseases are growing in prevalence and are in large part driven by lifestyle choices such as smoking, physical inactivity, unhealthy diet and the harmful use of alcohol. The metabolic imbalance caused by increased carbohydrates (sugars), fats and cholesterol can stimulate NLRP3 activation. This chronic, low-grade NLRP3-driven inflammation can then also contribute to type 2 #diabetes, non-alcoholic steatohepatitis (#NASH), degenerative aspects of ageing and the development of some cancers.


We can use our diet to inhibit NLRP3 activation and promulgation and reduce our NCDs risk. Beta-hydroxybutyrate (BHB) is a ketone the body produces in response to prolonged #fasting, high intensity #exercise or a #ketogenic diet and has been shown to inhibit NLRP3 activation. #BHB also reduces joint swelling, tissue inflammation and serum interleukin without compromising immunity. BHB is produced by the body, and independently of pharmaceutical intervention is being shown to inhibit NLRP3, meaning that modifying diet and lifestyle may be enough to treat NLRP3-mediated inflammatory diseases.


#NLRP3 research is vital as the number of individuals with these NCDs continues to rise as our ageing population increases.


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