Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases. 

Reference | CA20121

Execution date | 19/10/2021 – 18/10/2025

Non-communicable diseases (NCDs) account for 77% of all deaths in Europe and remain the most prevalent and without effective therapy.

The transcription factor NRF2 is a master regulator of multiple cytoprotective responses and a key molecular link among many NCDs. It provides a unique strategy for drug development and repurposing that is now starting to be translated to the pharmacological and clinical arena.

This Action will build a network of excellence for integrating and spreading the existing knowledge and providing innovative services, drugs and tools related to NRF2-pharmacology, with the final goal of boosting the translation to the European industry sector.

Development of NRF2-activating drugs for innovative therapies for Alzheimer's disease

Alzheimer’s disease (AD), the main cause associated with dementia, is the most prevalent neurodegenerative disease (NDD) nowadays, with more than 46 million people affected worldwide. Considering its direct relation with aging, this figure is estimated to surpass the amount of 100 million by year 2050. AD has a tremendous social impact, due to the loss of life quality and autonomy (both for the patient and their relatives / caregivers), and also a huge economic burden for national health systems, currently estimated at 818 billion dollars globally. Despite all the human and economic effort invested, in the last 15 years no new drugs have been incorporated to the clinical practice for the treatment of AD, and the efficacy of those that are commonly used is not satisfactory.

Interplay between neuroinflammation, oxidative stress and proteostasis: new targets to tackle neurodegeneration in AD (NewTargets4AD)

Among the different neurodegenerative diseases (NDDs), Alzheimers disease (AD) is the most common neurocognitive disorder with substantial social and economic impacts. To date, no new drug has qualified to be added to the current therapeutic arsenal that comprises cholinesterase inhibitors and the NMDA receptor antagonist memantine. There is accumulating knowledge indicating that chronic, unremitting, low grade neuroinflammation, oxidative stress, mitochondrial dysfunction and altered proteostasis/autophagy are interconnected processes that act in a coordinated and reverberating manner to cause neurodegeneration. We therefore hypothesize, that by acting on the latter systems, which are altered in the initial phases of neurodegeneration, the chances of having a better impact in preventing/reducing disease progression may be higher. In this context, the proposed project will focus on how certain enzymes such HO-1 (regulation of inflammation/oxidative stress), NADPH oxidase 4 (constitutive active enzyme responsible for producing reactive oxygen species) and PGC-alpha; (master regulator of mitochondrial biogenesis) impact on oxidative stress, neuroinflammation and autophagy flux markers to regulate neurodegeneration and dementia. 


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SAF2009-12150. Contribución de los receptores nicotínicos a la neuroprotección y a la neuroinflamación. MICINN. PI: Manuela G. López. 01/01/2010 – 31/12/2012.