Exploring the N-Benzylpiperidine and N, N-Dibenzyl(N-Methyl)amine fragments as privileged structures in the search of new multitarget directed drugs for Alzheimer's disease
Alzheimer’s disease (AD) is a neurodegenerative illness characterized by a progressive loss of neurons in specific areas, such as forebrain, neocortex and subcortical cholinergic projections from nucleus basalis of Meynert. Loss of cholinergic neurons entails low levels of acetylcholine (ACh); this...
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| Formato: | tesis doctoral |
| Fecha de publicación: | 2017 |
| País: | España |
| Recursos: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/22404 |
| Acesso em linha: | https://hdl.handle.net/20.500.14352/22404 |
| Access Level: | acceso abierto |
| Palavra-chave: | 615.27(043.2) 547(043.2) Alzheimer’s disease AD Enfermedad de Alzheimer EA Neurociencias (Medicina) Química farmaceútica Química orgánica (Farmacia) 2490 Neurociencias 2390 Química Farmacéutica |
| Resumo: | Alzheimer’s disease (AD) is a neurodegenerative illness characterized by a progressive loss of neurons in specific areas, such as forebrain, neocortex and subcortical cholinergic projections from nucleus basalis of Meynert. Loss of cholinergic neurons entails low levels of acetylcholine (ACh); this diminished amount of neurotransmitter is responsible for the disruption in the neuronal transmission between the cells involved in learning and memory processes. This interruption in neuronal communication is the origin of the cognitive symptoms of AD such as memory loss, incapacity to learn, to reason, to make judgments and failure to communicate. Understanding of disruption in cholinergic system led to acetylcholinesterase (AChE) as the first target in the search of therapeutic agents to treat AD. Acetylcholinesterase inhibitors (AChEi) were the first class of drugs successfully used in the symptomatic treatment of this disease. However, despite the improvement in cognitive and behavioral impairments in patients treated with AChEi’s, this kind of drugs is not able to stop the neurodegeneration. Explaining the origin of cognitive symptoms is not enough to understand the real cause of neurodegeneration in AD. Nowadays, beta-amyloid peptide (Aβ) is considered the initiating substance in the process leading to neuronal death. Insoluble Aβ fibrils are the main constituent of the senile plaques, which are considered the toxic element triggering the cascade of cellular responses that finally produce degeneration and death of neurons. Some of these events are neuro-inflammation, production of reactive oxygen species (ROS) and tau protein hyper phosphorylation... |
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