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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
Evaluación de fragmentos de N-Bencilpiperidina y N, N-Dibencil(N-metil)amina como estructuras privilegiadas en la búsqueda de nuevos fármacos multifuncionales para el tratamiento de la enfermedad de Alzheimer

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Estrada Valencia, Martín H. (2017) 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. [Thesis]

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Abstract

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...

Resumen (otros idiomas)

La enfermedad de Alzheimer (EA) es una patología que se caracteriza por una pérdida progresiva de neuronas en áreas específicas tales como la corteza frontal, el neocórtex, y las proyecciones subcorticales del nucleus basalis de Meynert. Dicha pérdida de neuronas colinérgicas produce niveles bajos de acetilcolina, ocasionando una interrupción de la transmisión entre las células implicadas en los procesos de memoria y aprendizaje. Esta interrupción es el origen de los síntomas cognitivos de la EA, tales como pérdida de memoria, incapacidad para pensar, para razonar y hacer juicios, así como dificultades de comunicación. El conocimiento de la disfunción en el sistema colinérgico condujo a proponer a la acetilcolinesterasa como la primera diana farmacológica en la búsqueda de agentes terapéuticos para el tratamiento del alzheimer. Los inhibidores de la acetilcolinesterasa fueron la primera clase de fármacos usados con éxito en el tratamiento sintomático de esta enfermedad. Sin embargo, a pesar de mejorar los indicadores cognitivos y comportamentales en pacientes tratados con inhibidores de acetilcolinesterasa, esta clase de fármacos ha sido incapaz de detener la degeneración neuronal...

Item Type:Thesis
Additional Information:

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Química Orgánica y Farmacéutica, leída el 05/05/2016

Directors:
DirectorsDirector email
Rodríguez Franco, María Isabel
Uncontrolled Keywords:Alzheimer’s disease, AD
Palabras clave (otros idiomas):Enfermedad de Alzheimer, EA
Subjects:Medical sciences > Medicine > Neurosciences
Medical sciences > Pharmacy > Pharmaceutical chemistry
Medical sciences > Pharmacy > Organic chemistry
ID Code:43715
Deposited On:30 Jun 2017 11:11
Last Modified:13 Dec 2018 09:46

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