Abstract
Not only physiological phenomena but also pathological phenomena can now be explained by the change of signal transduction in the cells of specific tissues. Commonly used cellular signal transductions are limited. They consist of the protein–tyrosine kinase dependent or independent Ras-ERK pathway, and the PI3K-Akt, JAK-STAT, SMAD, and NF-κB-activation pathways. In addition, biodegradation systems, such as the ubiquitin–proteasome pathway and autophagy, are also important for physiological and pathological conditions. If we can control signaling for each by a low-molecular-weight agent, it would be possible to treat diseases in new ways. At present, such cell signaling inhibitors are mainly looked for in plants, soil microorganisms, and the chemical library. The screening of bioactive metabolites from deep-sea organisms should be valuable because of the high incidence of finding novel compounds. Although it is still an emerging field, there are many successful examples, with new cell signaling inhibitors. In this review, we would like to explain the current view of the cell signaling systems important in diseases, and show the inhibitors found from deep-sea organisms, with their structures and biological activities. These inhibitors are possible candidates for anti-inflammatory agents, modulators of metabolic syndromes, antimicrobial agents, and anticancer agents.
Highlights
Nowadays most pathological phenomena such as inflammation, cancer, and diabetes mellitus can be explained by a change of signal transduction in the cells of specific tissues.if we could control the specific signal transductions in the body, it would be possible to ameliorate diseases using new concepts
We would like to explain the current view of the cell signaling systems important in diseases, and show the inhibitors found from deep-sea organisms, with their structures and biological activities
We have looked for the activators of cellular autophagy and have previously reported that the plant-derived alkaloid conophylline ameliorated cellular models of Parkinson’s and Huntington’s diseases by the activation of autophagy [17]
Summary
Nowadays most pathological phenomena such as inflammation, cancer, and diabetes mellitus can be explained by a change of signal transduction in the cells of specific tissues. If we could control the specific signal transductions in the body, it would be possible to ameliorate diseases using new concepts. There are several ways to control cellular signal transductions; they are gene-editing therapy; protein therapy, such as providing antibodies or growth factors; and chemotherapy using low molecular weight compounds. Signal transduction inhibitors of low molecular weight can be screened to antibiotics, anticancer agents, and enzyme inhibitors from nature. We explain signal transductions in relation to diseases, the methodology of inhibitor screening, screening sources past and present, and we describe examples of the isolation of cell signaling inhibitors from deep-sea organisms
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