Lecture entitled “NOS1AP, an adaptor protein linked to neurological diseases, reveals a novel signalling paradigm”
Venue: Albert L.T. 4pm 11th June 2015
Michael Courtney leads a research group focused on neuronal signaling mechanisms and is currently based at the Turku Centre for Biotechnology, Turku, Finland.
Research: After early investigations of the roles of
JNK signalling in neuronal death and development his group focused on
identifying targetable mechanisms by which NMDA receptor signaling influences
neuronal cell fate via activation of the p38MAPK pathway. One of the major NMDA
receptor pathways regulating p38MAPK involves the ternary complex of NMDA
receptor, PSD95 and nNOS. The lab demonstrated that PSD95/nNOS-dependent
pathways could be inhibited by nNOS-derived peptides, resulting in
neuroprotection. They showed that NMDA receptor activity leads to recruitment
of NOS1AP to nNOS and demonstrated that NOS1AP is required for NMDA-evoked
stress-activated MAPK responses and downstream excitotoxic consequences. They
developed a selective inhibitor peptide of the interaction between NOS1AP and
nNOS, with neuroprotective properties in cell cultures and in vivo (in a
preclinical model of perinatal asphyxia). More recently they identified that
interaction of nNOS with NOS1AP involves an unexpectedly complex interplay
between two distinct interaction sites. Each site is potentially druggable,
thereby providing increased opportunities for therapeutic intervention. This is
of potential interest considering that the NR-PSD95-nNOS complex and
potentially the recruitment of NOS1AP may be involved in some of the most
common causes of death and disability from stroke to neuropathic pain,
depression and anxiety disorders, while NOS1AP has been genetically linked to
schizophrenia, post-traumatic stress disorder, sudden cardiac death and long QT
syndromes. http://www.btk.fi/research/affiliated-groups/courtney-michael-neuronal-signal-pathways
All welcome to attend,
Jochen Prehn