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Signaling Pathways in Inflammation and Anti-inflammatory Therapies
Yiu To Yeung1, Faisal Aziz1, Angelica Guerrero-Castilla2
1China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
Abstract:
During the past decade, an abundance of new evidence highlighted the importance of inflammation in the development of chronic pathologies such as neurodegeneration, cancer, diabetes, cardiovascular disease and inflammatory bowel disease. However, most of the current therapies do not address the underlying problem and better therapies are urgently needed. A growing number of researchers have discovered various signaling pathways that are associated with the initiation and progression of inflammation. Among different pathways, we will focus on three classical inflammatory pathways: p38 MAPK, IL-6/JAK/STAT3 and PI3K; and a non-classical inflammatory pathway, the Hippo. Recently, the Hippo pathway has been linked to various inflammatory modulators such as FoxO1/3, TNFα, IL-6, COX2, HIF-1α, AP-1, JAK and STAT. In this review, the molecular mechanisms, associated pathologies and selected drugs (both preclinical and clinical) of these signaling pathways will be summarized. Finally, limitations and potential risks of anti-inflammatory drugs will also be discussed.
Insights
Inflammation drives chronic diseases, but current therapies are insufficient. This review explores key inflammatory signaling pathways, including Hippo, and their therapeutic potential for better treatments.
Area of Science:
- Biomedical Science
- Molecular Biology
- Immunology
Background:
- Inflammation is a key factor in chronic diseases like neurodegeneration, cancer, and cardiovascular disease.
- Existing therapies often fail to address the root causes of inflammation, necessitating novel therapeutic strategies.
Purpose of the Study:
- To review the molecular mechanisms of classical inflammatory pathways (p38 MAPK, IL-6/JAK/STAT3, PI3K) and the non-classical Hippo pathway.
- To summarize associated pathologies and current/emerging drugs targeting these pathways.
- To discuss limitations and risks of anti-inflammatory drug therapies.
Main Methods:
- Literature review of signaling pathways involved in inflammation.
- Analysis of molecular mechanisms, associated pathologies, and drug development (preclinical and clinical).
- Focus on p38 MAPK, IL-6/JAK/STAT3, PI3K, and Hippo pathways, including their interactions with inflammatory modulators.
Main Results:
- Detailed overview of the molecular intricacies of selected inflammatory signaling pathways.
- Identification of potential therapeutic targets within these pathways for various chronic diseases.
- Discussion of the role of the Hippo pathway as a novel target in inflammation research.
Conclusions:
- Understanding these inflammatory pathways is crucial for developing effective treatments.
- The Hippo pathway presents a promising, yet under-explored, target for anti-inflammatory therapies.
- Careful consideration of drug limitations and risks is essential for safe and effective clinical application.
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