Unfortunately due to unforeseen circumstances this seminar (originally scheduled for Wednesday 13th July) has been postposed. Further details regarding the rescheduled date will be published in due course.
Title: “Targeted cAMP degradation by PDE4: therapeutic action and potential in inflammatory disease, prostate cancer, schizophrenia, depression, acrodystosis, weight and sleep disorders and ADPKD”
Speaker: Professor Miles Houslay, Institute of Pharmaceutical Science King’s College London and Mironid Ltd, BioCity, Scotland.
Abstract: Cells are constantly bombarded by environmental cues, be they chemical, electrical or mechanical. These inputs are integrated to generate coordinated responses that are intimately connected with spatially discrete changes occurring within the 3-D cell envelope. Thus functional outcomes are formulated in both time and space. The discovery of cAMP transformed our understanding of cellular regulation by providing not only the ‘second messenger’ concept, but also the discovery of G-proteins, the G protein-coupled receptor (GPCR) superfamily and, importantly, the conceptual roots of compartmentalized signalling.
Targeted degradation of cAMP by PDE4 cAMP phosphodiesterases plays a pivotal role in underpinning compartmentalised cAMP signalling in cells. Sequestered PDE4 isoforms act to sculpt gradients of cAMP surrounding specific signalling complexes. In this way, the activation threshold of cAMP effectors in spatially defined intracellular complexes can be regulated so as to control distinct physiological actions. Thus selective inhibition of PDE species offers considerable therapeutic potential, as demonstrated by the PDE4 selective inhibitor, apremilast (OtlezlaR), which was recently approved as a oral therapy for treating psoriatic arthritis.
PDE4 isoform diversity, targeting and regulation will be discussed and implications for therapy and diagnostics relating to inflammatory disease, prostate cancer, schizophrenia, depression, acrodystosis, weight and sleep disorders and ADPKD.
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