Hybride Molecules for the Treatment of Alzheimer´s Disease

Alzheimer`s disease (AD) is the most prevalent form of senile dementia, responsible for 60-80% of cases in individuals aged 65 and above. This neurodegenerative disease leads to severe and irreversible effects, including cognitive decline, memory loss, behavioural changes, depression, psychosis, and Parkinsonian symptoms, ultimately resulting in complete dependence on caregivers. According to the World Alzheimer Report 2019, by 2025 approximately 80 million people worldwide will be affected by dementia, and this number is projected to reach 150 million by 2050, which is a concerning trend. Therefore, the WHO has designated AD as a priority in public health. While there is currently no cure, ongoing research aims to develop effective treatments to slow or prevent the disease. Scientists are exploring genetic factors, environmental influences, and potential drug therapies to better understand and combat Alzheimers. Early diagnosis and lifestyle interventions can help manage symptoms and improve the quality of life for those affected. Traditional treatments targeting single aspects of the disease have proven inadequate. This has led to explore multitarget strategies that address several pathological factors simultaneously. In this context, this project is dedicated to the development of dual/hybrid compounds as a comprehensive response to the multifaceted pathophysiology of AD. This means, that within one molecule two biological receptors, responsible for the progression of Alzheimers disease, can be addressed. We hypothesize that the fusion of two biological targets related to Alzheimers disease within a single molecule promises synergistic enhancement of pharmacological activities and diminished toxicity. The molecules designed, synthesised and biologically investigated from this project have the potential to simultaneously modulate multiple critical biological targets involved in AD progression. The project will be conducted in a collaboration between Graz University of Technology and the Institute of Microbiology of the Czech Academy of Science in Prague. The dedicated compounds will be synthesised in Graz and biologically evaluated upon their properties to be active against Alzheimer progression will be undertaken in Prague.