4.3 Article

Adenoviral expression of CREB protects neurons from apoptotic and excitotoxic stress

Journal

NEUROREPORT
Volume 15, Issue 7, Pages 1171-1175

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00001756-200405190-00018

Keywords

adenoviral; CREB; glutamate; hippocampal; ischemia; neurodegeneration

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Funding

  1. Biotechnology and Biological Sciences Research Council [C18365] Funding Source: researchfish
  2. Biotechnology and Biological Sciences Research Council [C18365] Funding Source: Medline
  3. Wellcome Trust [069280] Funding Source: Medline

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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.

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