Exploring the Role of CD36 in Nonalcoholic Steatohepatitis (NASH)
Nonalcoholic steatohepatitis (NASH) is a progressive liver condition characterized by inflammation, cell damage and fibrosis. NASH affects up to 6% of the United States population, and is becoming a significant health concern. Statistics indicate that up to 10% of individuals diagnosed with NASH will develop cirrhosis, causing permanent liver damage.
Nonalcoholic Steatohepatitis (NASH)
Nonalcoholic steatohepatitis (NASH) is a progressive liver condition characterized by inflammation, cell damage and fibrosis. NASH affects up to 6% of the United States population,¹ and is becoming a significant health concern. Statistics indicate that up to 10% of individuals diagnosed with NASH will develop cirrhosis,² causing permanent liver damage.
Immune response plays a crucial role in NASH. The interaction between immune cells and liver cells contributes to the inflammation observed in NASH. This inflammatory response triggers the release of pro-inflammatory molecules, further promoting liver cell damage and fibrosis. Despite the increasing incidence of NASH, there are currently no FDA-approved therapies to treat it. Here we use Causaly to better understand genetic alterations associated with NASH.
Genes and Proteins Affecting NASH
Around 2000 genes and proteins which affect NASH have been reported, according to Causaly. Almost 400 of these targets affect NASH pathophysiology only when mutated or dysregulated. In this use case, we have zeroed in on antigen mutations associated with NASH due to their involvement in immune response. Refining by the strength of the target-disease relationship, platelet glycoprotein 4, also known as CD36, was identified as a protein of interest in NASH in the last 5 years (Figure 1).
The Role of Platelet Glycoprotein 4 (CD36) in NASH
CD36 is an integral glycoprotein found on the surface of various cells, including immune cells, adipocytes and endothelial cells. This protein has key functions in fatty acid uptake, inflammation and immune response and its overexpression has been implicated in NASH.³
A 2018 study showed that palmitoylation plays a crucial role in controlling the distribution and functions of CD36 in NASH.⁴ This research showed that blocking palmitoylation of CD36 reduced its distribution in hepatocyte plasma membranes, thus, protecting mice from NASH. More recently, research showed CD36 induced inflammatory response, causing NASH to progress into liver cancer, cirrhosis, or hepatocellular carcinoma.⁵ Ongoing trials are studying how platelets contribute to NAFLD and NASH and to better understand platelet activation and signaling pathways.⁶
Biochemical Pathways Affected by CD36 in NASH
Using Causaly, we can uncover the target biology, and look for cellular and molecular downstream cascades of CD36 in NASH:
The development of targeted and personalized treatment is highly dependent on our understanding of the genetic and molecular pathways underlying conditions. Researchers can pinpoint specific genes and proteins, like CD36 in NASH, that aid in the development of diseases by unravelling these complex networks. This information paves the way for the creation of diagnostic, prognostic, and therapeutic approaches that are more successful.
To find out more about how you can use Causaly to accelerate your research, request a demo here.
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