Network pharmacology for mechanistically redefined comorbidities

Mahmoud (Hassan Mahmoud) Elbatrik

Research output: ThesisDoctoral ThesisInternal

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Abstract

Diabetes, hypertension and stroke are common comorbidities and the leading causes of death. Current therapies are symptom-oriented and are imprecise. One main reason for this is that these complex diseases are defined by a symptom in an organ and not by a molecular mechanism. Network medicine, however, shows that within the diseasome these comorbidites relate to the same cluster and, thus, likely share common causal pathomechanisms. Targeting these mechanisms would be preferred to symptomatic therapy and, since these mechanisms are small signalling modules, network pharmacology is preferable to single-target approaches. One example of such a causal signalling module is the reactive oxygen species (ROS) and cGMP signaling (ROCG) network. We have validated this mechanism in a subgroup of hypertensive patients and in NADPH oxidase 5 (NOX5)-knock in mice where NOX5 induced NO synthase uncoupling as a causal mechanism to induce age-related hypertension.
Original languageEnglish
Awarding Institution
  • Maastricht University
Supervisors/Advisors
  • Schmidt, Harald, Supervisor
  • Casas Guijarro, Ana, Advisor
Award date26 Aug 2020
Place of PublicationMaastricht
Publisher
Print ISBNs9789464023268
DOIs
Publication statusPublished - 2020

Keywords

  • network pharmacology
  • mechanism-based therapeutics
  • mechanism-based therapeutics biomarkers
  • systems Medicine

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