ADIT - Design of small molecule therapeutics for the treatment of Alzheimer's disease on the discovery of innovative drug targets.' (Life sciences, genomics and biotechnology for health) (2005-06-01 - 2010-05-31) (»add to infobox)

Alzheimer's disease (AD) is the most common neurodegenerative disease. The unmet needs (medical, social and economic) in AD are enormous. This proposal focuses on the development to the preclinical stage of novel chemical entities endowed with specific neuroprotective activity in AD and capitalizes on the most widely accepted view on the etiology of AD. A validated in vitro model of Aß neurotoxicity, established transcriptomics and proteomics methodologies and sophiscated bioinformatic tools are used in order to identify proteins causally involved in Aß-mediate neurodegeneration. An efficient drug discovery pipeline, including stringent target validation based on in vitro, in vivo and ex vivo approaches, will be employed to bring two drug candidates to the clinic. The differentiators in this proposal lie in the target identification part of the project and in the capacity to materialize fundamental insights of mechanisms of action into drug candidates for clinical testing, and can be summarized as a) the strategy (emphasis on the early, initial response of the neuronal culture to Aß; b) the approach (emphasis on the analysis of differential protein phosphorylation in order to identify signal transduction components and on DNA microarray analysis in order to identify the first wave of transcriptional response); c) the analysis, (bioinformatics is employed to merge Proteomics and Transcriptomics data into a coherent view of Aß-mediated signal transduction in neurons to generate"pathopathways"); d) the drug discovery expertise to convert knowledge into potential therapies. The partners in this integrated project have been selected for their specific competencies in the different contribution areas, and the presence of an SME as project coordinator will ensure a milestone-driven progression of the project and the translation of scientific findings into the reality of drug discovery.' Keywords: Alzheimer's Disease, signal transduction, pathway analysis, biological target, drug discovery'

COORDINATOR (1/1)

PARTICIPANTS (8/8)

RELATED THEMATIC AREAS (1/1)