Non-conventional target approach for drug discovery against neurodegenerative diseases: Nrf2 upregulation

Objective

As a result of the aging population of the developed countries, neurodegenerative diseases (NDD) afflict an ever-increasing number of people. Alzheimer’s disease (AD) is the most prevalent NDD with more than 36 million people currently affected worldwide. Although AD has been studied for more than a hundred years, its “ultimate” trigger is not yet completely understood. Focus for over two decades on amyloid beta (Aβ) and tau protein, as targets to develop a neuroprotective medicine to delay Alzheimer’s disease (AD) progression, has so far failed. AD is developed as an extremely complex network of events, a fact that has led to the proposal of the “multifactorial hypothesis”. AD, to be defined, must be seen as interconnected processes, rather than independent pathways triggering the final consequences of the disease. In considering the genetic target-based approach, it should be taken into account that familial AD is less than 1%; thus, at least 99% of patients suffer a sporadic form of AD. It seems therefore reasonable to follow non-genetic approaches. For instance, the free radical theory implies progressive cell damage with age, leading to enhanced mitochondrial DNA mutations, futile mitochondrial Ca2+ cycling with excess ATP consumption, oxidative stress and ensuing mitochondrial dysfunction. Based on these observations, the objective in this proposal is the design of selective “multi-target drugs” able to modify two or more key steps in different AD related pathological pathways. By mixing several targets with tuneable properties in one molecule it will be possible to affect several pathways at once and therefore, affecting “redundancy” processes underlying AD. Non conventional selected target will be auto-defensive pathways (phase II gene expression) within the cell and the known targets that are known to be important in AD pathology. This multi-disciplinary approach will combine organic chemistry in order to develop novel structures with optimized properties.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.

• medical and health sciences basic medicine pharmacology and pharmacy drug discovery
• medical and health sciences basic medicine neurology dementia alzheimer
• natural sciences chemical sciences organic chemistry
• natural sciences biological sciences genetics mutation
• medical and health sciences basic medicine pathology

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• 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)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• FP7-PEOPLE-2012-CIG - Marie-Curie Action: "Career Integration Grants"

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2012-CIG
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

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

Coordinator