GPCRs Are Optimal Regulators of Complex Biological Systems and Orchestrate the Interface between Health and Disease


Leysen H., Walter D., Christiaenssen B., Vandoren R., Harputluoglu I., Van Loon N., ...Daha Fazla

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, cilt.22, sa.24, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Sayı: 24
  • Basım Tarihi: 2021
  • Doi Numarası: 10.3390/ijms222413387
  • Dergi Adı: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: dimensionality, G protein-coupled receptor, network, pharmacology, precision, quantitative, therapeutic, DNA damage, allostasis, systems biology, PROTEIN-COUPLED RECEPTORS, BETA(2) ADRENERGIC-RECEPTOR, DIRECTED ACYCLIC GRAPHS, HEART-RATE-VARIABILITY, MU-OPIOID RECEPTOR, NETWORK MEDICINE, BETA(2)-ADRENERGIC RECEPTOR, CONSTITUTIVE ACTIVITY, MOLECULAR SIGNATURES, ALZHEIMERS-DISEASE
  • Orta Doğu Teknik Üniversitesi Adresli: Hayır

Özet

GPCRs arguably represent the most effective current therapeutic targets for a plethora of diseases. GPCRs also possess a pivotal role in the regulation of the physiological balance between healthy and pathological conditions; thus, their importance in systems biology cannot be underestimated. The molecular diversity of GPCR signaling systems is likely to be closely associated with disease-associated changes in organismal tissue complexity and compartmentalization, thus enabling a nuanced GPCR-based capacity to interdict multiple disease pathomechanisms at a systemic level. GPCRs have been long considered as controllers of communication between tissues and cells. This communication involves the ligand-mediated control of cell surface receptors that then direct their stimuli to impact cell physiology. Given the tremendous success of GPCRs as therapeutic targets, considerable focus has been placed on the ability of these therapeutics to modulate diseases by acting at cell surface receptors. In the past decade, however, attention has focused upon how stable multiprotein GPCR superstructures, termed receptorsomes, both at the cell surface membrane and in the intracellular domain dictate and condition long-term GPCR activities associated with the regulation of protein expression patterns, cellular stress responses and DNA integrity management. The ability of these receptorsomes (often in the absence of typical cell surface ligands) to control complex cellular activities implicates them as key controllers of the functional balance between health and disease. A greater understanding of this function of GPCRs is likely to significantly augment our ability to further employ these proteins in a multitude of diseases.