A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Mechanisms of NOS1AP action on NMDA receptor-nNOS signaling
Tekijät: Courtney MJ, Li LL, Lai YY
Kustantaja: FRONTIERS RESEARCH FOUNDATION
Kustannuspaikka: Switzerland
Julkaisuvuosi: 2014
Journal: Frontiers in Cellular Neuroscience
Tietokannassa oleva lehden nimi: FRONTIERS IN CELLULAR NEUROSCIENCE
Lehden akronyymi: FRONT CELL NEUROSCI
Artikkelin numero: 252
Vuosikerta: 8
Sivujen määrä: 7
ISSN: 1662-5102
eISSN: 1662-5102
DOI: https://doi.org/10.3389/fncel.2014.00252
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/18498644
NMDA receptors (NMDAR) are glutamate-gated calcium channels that play pivotal roles in fundamental aspects of neuronal function. Dysregulated receptor function contributes to many disorders. Recruitment by NMDARs of calcium-dependent enzyme nNOS via PSD95 is seen as a key contributor to neuronal dysfunction nNOS adaptor protein (NOS1AP), originally described as a competitor of PSD95:nNOS interaction, is regarded an inhibitor of NMDAR-driven nNOS function. In conditions of NMDAR hyperactivity such as excitotoxicity, one expects NOS1AP to be neuroprotective. Conditions of NMDAR hypoactivity, as thought to occur in schizophrenia, might be exacerbated by NOS1AP. Indeed GWAS have implicated NOS1AP and nNOS in schizophrenia. Several studies now indicate NOS1AP can mediate rather than inhibit NMDAR/nNOS-dependent responses, including excitotoxic signaling. Yet the concept of NOS1AP as an inhibitor of nNOS predominates in studies of human disease genetics. Here we review the experimental evidence to evaluate this apparent controversy, consider whether the known functions of NOS1AP might defend neurons against NMDAR dysregulation and highlight specific areas for future investigation to shed light on the functions of this adaptor protein.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
