The role of DREAM in synaptic dysfunction in Alzheimer's disease

Project Information

DREAM IN AD

Grant agreement ID: 303701

Project closed

Start date 15 September 2012

End date 14 February 2015

Funded under

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Total cost € 60 416,66

EU contribution € 60 416,66

Coordinated by

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain

Objective

Alzheimer's disease (AD) is the most common form of age-related dementia. This neurodegenerative disorder is characterized by massive neuronal death and deposition of amyloid-β peptide (Aβ), which is formed by processing of amyloid precursor protein (APP). The mechanism of neuronal degeneration in AD are not well understood, but growing evidence shown that neuronal death is at least in part due to dysregulated Ca2+ signalling.
Calsenilin/DREAM was identified as a Ca2+-binding protein that interacts with presenilins, serves as a transcription repressor, and binds to the A-type potassium channel. Ca2+-insensitive DREAM mutants or DREAM mutants with an altered capability to regulate transcription will modify Ca2+ homeostasis and synaptic plasticity. Previous findings suggest that DREAM/calsenilin is involved in apoptosis and Aβ production. However, high levels of DREAM/calsenilin were found in the cortex of AD brains and in the neocortex and the hippocampus of Swedish mutant APP (APPswe) transgenic mice brains.
The general objective of the project is to elucidate the role of DREAM/calsenilin on the progression of synaptic dysfunction. The specific objectives for the project are:
-To study of DREAM and DREAM mutants in regards to AD-related markers of AD.
-Analysis of DREAM expression in brains from different transgenic models of AD.
-To assess the functional consequences of mutant DREAM overexpression in the development of AD in animal models overexpressing mutant human APP
-Effect of DREAM deletion in the development of AD.
-Integration of the information obtained in post-mortem material from AD patients.
-To screen molecules able of interacting with DREAM for their potential therapeutic effect.
As a result of this study, the synaptic dysfunction associated to neurodegenerative processes may be modified, suggesting potential new targets for human drug development based on DREAM function.

Fields of science

• medical and health sciences › basic medicine › pharmacology and pharmacy › drug discovery
• medical and health sciences › basic medicine › neurology › dementia › alzheimer
• natural sciences › chemical sciences › inorganic chemistry › alkali metals
• natural sciences › biological sciences › biochemistry › biomolecules › proteins
• medical and health sciences › basic medicine › physiology › homeostasis

Programme(s)

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

• FP7-PEOPLE-2011-CIG - Marie-Curie Action: "Career Integration Grants"

Call for proposal

FP7-PEOPLE-2011-CIG
See other projects for this call

Funding Scheme

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS

• EU contribution: € 60 416,66
• Address: CALLE SERRANO 117 ; 28006 Madrid ; Spain
• Region: Comunidad de Madrid › Comunidad de Madrid › Madrid
• Activity type: Research Organisations
• Administrative Contact: Alberto Sereno álvarez (Prof.)
• Total cost: No data