Publication: Síntesis y evaluación de ligandos tau-selectivos basados en estructuras de oxindol como potenciales agentes de imagen PET para diagnóstico in vivo de la Enfermedad de Alzheimer y otras tauopatías
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2022-06-23
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Universidad Complutense de Madrid
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Abstract
La enfermedad de Alzheimer (EA) pertenece a un grupo de patologías denominadas tauopatías. Actualmente, más de 24 millones de personas padecen esta enfermedad así como otras demencias, lo que representa un serio problema de salud, especialmente si tenemos en cuenta que el diagnóstico de la EA sólo puede confirmarse de forma certera a través de un análisis histopatológico post mortem. Por tanto son necesarias técnicas no invasivas que sean efectivas para el diagnóstico precoz de la EA. La EA presenta dos biomarcadores principales: la proteina tau y el péptido amiloide (Aβ). La proteina tau es la principal Proteína Asociada a Microtúbulos (MAP) siendo responsable de la estabilización axonal que permite el adecuado transporte neuronal. En su forma aberrante, la proteina tau sufre un proceso de hiperfosforilación que conduce a su agregación anormal en dos tipos de estructuras tóxicas principales, los PHFs (del inglés Paired Helicoidal Filaments) y los NFTs (del inglés Neurofibrillary Tangles) presentes en el medio intraneuronal. Este fenómeno implica la pérdida de la actividad biológica de tau y en consecuencia, el deterioro cognitivo que sufren los pacientes debido a la muerte neuronal asociada. El péptido amiloide, por su parte también sufre procesos de agregación aberrante, que en su caso conducen a la formación de las conocida Placas Seniles (SPs) extracelulares, presentes en los pacientes de EA y que desencadenan procesos de respuesta inflamatoria local...
Alzheimer ’s disease (AD) belongs to the pathology group named Taupathies. Currently, more than 24 million people suffer from Alzheimer disease and other dementias. This represents a serious health problem, especially if we take into account that the diagnosis of AD can only be confirmed by a postmortem histological analysis. So we need more effective and non-invasive techniques for early diagnosis.AD presents two biomarkers: tau protein and amyloid β peptide. Tau protein is the main microtubule-associated protein, responsible for axonal stabilization, which allows the proper neuronal transport. In its aberrant form, tau undergo a process of hyperphosphorilation that leads to an abnormal aggregation, forming Paired Helicoidal Filaments (PHFs) and Neurofibrillary Tangles (NFTs) in the intraneuronal medium. This process drives to the loss of the biological activity of tau and as a consequence, the cognitive decline. In addition, the other biomarker in Alzheimer's disease, the β-amyloid peptide aggregates as an extracellular deposit, forming senile plaques (SPs), which can trigger a local inflammatory response...
Alzheimer ’s disease (AD) belongs to the pathology group named Taupathies. Currently, more than 24 million people suffer from Alzheimer disease and other dementias. This represents a serious health problem, especially if we take into account that the diagnosis of AD can only be confirmed by a postmortem histological analysis. So we need more effective and non-invasive techniques for early diagnosis.AD presents two biomarkers: tau protein and amyloid β peptide. Tau protein is the main microtubule-associated protein, responsible for axonal stabilization, which allows the proper neuronal transport. In its aberrant form, tau undergo a process of hyperphosphorilation that leads to an abnormal aggregation, forming Paired Helicoidal Filaments (PHFs) and Neurofibrillary Tangles (NFTs) in the intraneuronal medium. This process drives to the loss of the biological activity of tau and as a consequence, the cognitive decline. In addition, the other biomarker in Alzheimer's disease, the β-amyloid peptide aggregates as an extracellular deposit, forming senile plaques (SPs), which can trigger a local inflammatory response...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, leída el 29-03-2022