Adenoviral expression of CREB protects neurons from apoptotic and excitotoxic stress.
In this study we have used a molecular approach to manipulate CREB gene expression to study its role in the regulation of neuronal cell death. To achieve this, adenoviral (Ad) vectors encoding EGFP, CREB, and a powerful CREB dominant-negative, known as A-CREB were constructed. The over-expression of CREB but not A-CREB was found to protect primary hippocampal neurons from staurosporine-induced apoptosis, glutamate induced excitotoxicity and exposure to an in vitro ischaemic stress. Hence, manipulating CREB-regulated pathways may provide a means of delaying or preventing the neuronal cell death associated with ischaemic related injury, and in neurodegenerative diseases such as Huntington's and Alzheimer's disease.
Glover
Colin P J
CP
The Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE), Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
Heywood
Darren J
DJ
Bienemann
Alison S
AS
Deuschle
Ulrich
U
Kew
James N C
JN
Uney
James B
JB
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis* / Q000235:genetics; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006367:HeLa Cells; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D018690:Excitatory Amino Acid Agonists