Multiorgan locked-state model of chronic diseases and systems pharmacology opportunities.

Drug Discov Today

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Published: January 2024

With increasing human life expectancy, the global medical burden of chronic diseases is growing. Hence, chronic diseases are a pressing health concern and will continue to be in decades to come. Chronic diseases often involve multiple malfunctioning organs in the body. An imminent question is how interorgan crosstalk contributes to the etiology of chronic diseases. We conceived the locked-state model (LoSM), which illustrates how interorgan communication can give rise to body-wide memory-like properties that 'lock' healthy or pathological conditions. Next, we propose cutting-edge systems biology and artificial intelligence strategies to decipher chronic multiorgan locked states. Finally, we discuss the clinical implications of the LoSM and assess the power of systems-based therapies to dismantle pathological multiorgan locked states while improving treatments for chronic diseases.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11109989PMC
http://dx.doi.org/10.1016/j.drudis.2023.103825DOI Listing

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