Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Disrupted in schizophrenia 1 and phosphodiesterase 4B: towards an understanding of psychiatric illness
Ist Teil von
The Journal of physiology, 2007-10, Vol.584 (2), p.401-405
Ort / Verlag
Oxford, UK: The Physiological Society
Erscheinungsjahr
2007
Link zum Volltext
Quelle
Wiley Online Library Journals Frontfile Complete
Beschreibungen/Notizen
Disrupted in schizophrenia 1 (DISC1) is one of the most convincing genetic risk factors for major mental illness identified
to date. DISC1 interacts directly with phosphodiesterase 4B (PDE4B), an independently identified risk factor for schizophrenia.
DISC1âPDE4B complexes are therefore likely to be involved in molecular mechanisms underlying psychiatric illness. PDE4B hydrolyses
cAMP and DISC1 may regulate cAMP signalling through modulating PDE4B activity. There is evidence that expression of both genes
is altered in some psychiatric patients. Moreover, DISC1 missense mutations that give rise to phenotypes related to schizophrenia
and depression in mice are located within binding sites for PDE4B. These mutations reduce the association between DISC1 and
PDE4B, and one results in reduced brain PDE4B activity. Altered DISC1âPDE4B interaction may thus underlie the symptoms of
some cases of schizophrenia and depression. Factors likely to influence this interaction include expression levels, binding
site affinities and the DISC1 and PDE4 isoforms involved. DISC1 and PDE4 isoforms are targeted to specific subcellular locations
which may contribute to the compartmentalization of cAMP signalling. Dysregulated cAMP signalling in specific cellular compartments
may therefore be a predisposing factor for major mental illness.