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

Journal: Drug discovery today
PMID:

Abstract

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.

Authors

  • Choong Yong Ung
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA.
  • Cristina Correia
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine and Science, Mayo Clinic, 200 First, Street SW, Rochester, MN 55905, USA.
  • Hu Li
    School of Business, Qingdao University, Qingdao, Shandong, China.
  • Christopher M Adams
    Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
  • Jennifer J Westendorf
    Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA; Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
  • Shizhen Zhu
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA.