Targeting Circadian Clock Dysfunction in Alzheimer’s Disease

Recent Nobel Prize-winning discoveries on circadian clock (CC) have laid the foundation for ground-breaking approaches to treat many diseases, including Alzheimer’s disease (AD). AD is a current public health priority. Amplifying the demographic burden of the rising numbers of patients is the low success rate of AD therapies. Given that CC genes regulating memory, sleep, and neurodegeneration have altered expression profiles in AD, CC has recently emerged as a viable therapeutic target for new effective drugs. However, how to develop them remains a fundamental challenge. The “Targeting Circadian Clock Dysfunction in Alzheimer’s Disease” Doctoral Network (TClock4AD) is proposed to create a new generation of researchers able to face such challenge by harnessing neurobiology, medicinal chemistry, pharmaceutical nanotechnology, neuroimmunology, big data, bioinformatics, and entrepreneurship. TClock4AD will exploit unique expertise and advanced technologies at 10 leading universities, 3 research centers, a hospital, 10 non-academic institutions including SMEs, a large pharma company, a Health industry association, and a patient organization across EU, UK, Israel, USA and China. TClock4AD will deliver double degrees to 15 doctoral candidates, with triple-i knowledge/skills, broad vision and a business-oriented mindset. Their research activities will be structured around 5 scientific themes to: (1) develop novel artificial intelligence-, proteolysis targeting chimeras- and multitarget-based strategies for new CC drug candidates (2) develop novel drug delivery nanotechnologies, which take into consideration CC (3) investigate innovative in vitro (stem-cells, 3D cultures) & in vivo (Drosophila), as well as organ-on-chip techniques, for preclinical validation of CC drugs (4) get insight into the molecular mechanisms underlying CC in AD and associated drug response in mice and C. elegans models (5) develop innovative biotech business model and exploitation strategies.