Multifunctional Ligands Against Alzheimer's Disease

Dear Colleagues,

Over 100 years ago, Dr. Alois Alzheimer described an unknown brain disorder that today bears his name. Alzheimer’s disease is a progressive, incurable, and complex neurodegenerative disease that affected over 30 million people worldwide in 2018. The main hallmarks of the disease, found in the brains of Alzheimer’s patients, are deposits of beta-amyloid aggregates (senile plaques) that are located outside neurons, and twisted strands of protein tau (neurofibrillary tangles) that are located inside neurons. These pathological changes develop in the brain regions that are related to the memory and cognitive functions. As the cholinergic system is associated with memory and cognition, impaired cholinergic neurotransmission induces symptoms of cognitive decline and memory impairment in AD patients. Moreover, the pathogenesis of the disease includes excitotoxicity, neuroinflammation, mitochondria damage, oxidative stress, and metal ion dysregulation, which lead to a massive damage of neurons, synaptic dysfunction, neuronal death, and finally, to advanced dementia. At present, there is no available treatment that may slow down or stop the neurons’ damage and death.

As a result of the multiple factors that cause Alzheimer’s disease as well as the identification of many potential biological targets, a multi-target approach has been applied in search for potential drugs. Its goal is to create a single molecule, called a multifunctional ligand, that can interact selectively with several of the desired biological targets relevant for the disease. This strategy has been successfully developed since 2000, based on the observation that many marketed drugs are substantially promiscuous agents. The development of multifunctional ligands as potential anti-Alzheimer’s drugs has also accelerated over the recent years. This Special Issue aims to provide a forum for the presentation and dissemination of the results of the design, synthesis, and biological evaluation of novel multifunctional compounds against Alzheimer's disease. It is a very attractive topic; thus, we expect that this Special Issue will be a good platform for sharing our research results.

Prof. Dr. Barbara Malawska
Guest Editor

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