Emmanuel Atta Afriyie

Abstract Targeted protein degradation/downregulation (TPD/TPDR) is a disruptive paradigm for developing therapeutics. <2% of ~600 E3 ligases have been exploited for this modality, and efficacy for multi-subunit ion channels has not been demonstrated. NEDD4-2 E3 ligase regulates myriad ion channels, but its utility for TPD/TPDR is uncertain due to complex regulatory mechanisms.

Abstract Targeted recruitment of E3 ubiquitin ligases to degrade traditionally undruggable proteins is a disruptive paradigm for developing new therapeutics. Two salient limitations are that <2% of the ~600 E3 ligases in the human genome have been exploited to produce proteolysis targeting chimeras (PROTACs), and the efficacy of the approach has not been demonstrated for a vital class of complex multi-subunit membrane proteins - ion channels.

PHC is an essential health care based on practical, scientifically sound and socially acceptable methods and technology made universally accessible to individuals and families in a community through their full participation and at a cost affordable to them. PHC includes but not limited to basic medical curative care at the community, sub-district and district level. It focuses on promoting health and preventing illness.