Muñoz Madrigal, José LuisLópez Gutiérrez, Irene2024-02-192024-02-192024-02-19https://hdl.handle.net/20.500.14352/101550Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 23-06-2023La enfermedad de Alzheimer (EA) constituye la forma más común de demencia en todo el mundo y se prevé que su prevalencia aumente exponencialmente en los próximos años, mientras que aún no existen tratamientos eficaces que modifiquen el curso de esta enfermedad.La EA se caracterizada por la presencia de placas de amiloides, formadas por el péptido β-amiloide (Aβ), y de ovillos neurofibrilares (NFTs), formados por la proteína tau fosforilada, que llevan a la degeneración de las células nerviosas y atrofia cerebral. En los últimos años se ha demostrado el papel central de la neuroinflamación y la respuesta celular aberrante, particularmente de las células gliales, en la fisiopatología de la EA. Además, diversos estudios han demostrado la existencia de una pérdida temprana de neuronas noradrenérgicas en el locus coeruleus (LC), principal fuente de noradrenalina (NA) en el sistema nervioso central (SNC), y de la inervación noradrenérgica en las diferentes regiones cerebrales en la EA, lo que conlleva una compleja desregulación del sistema noradrenérgico en esta enfermedad neurodegenerativa...Alzheimer's disease (AD) is the most common form of dementia worldwide and its prevalence is expected to increase exponentially in the coming years, while there are still no effective treatments to modify the course of this disease.AD is characterized by the presence of amyloid plaques, formed by amyloid β peptide (Aβ), and neurofibrillary tangles (NFTs), formed by phosphorylated tau protein, leading to nerve cell degeneration and brain atrophy. In recent years, the central role of neuroinflammation and aberrant cellular response, particularly of glial cells, in the pathophysiology of AD has been described. In addition, several studies demonstrate the existence of an early loss of noradrenergic neurons in the locus coeruleus (LC), the main source of noradrenaline (NA) in the central nervous system (CNS), and of noradrenergic innervation in the different brain regions in AD, leading to a complex dysregulation of the LC-NA system in this neurodegenerative disease.On the other hand, different studies showed the neuroprotective potential of NA due to the reduction of proinflammatory molecules and the induction of neurotrophic factors through the control of glial cells. Based on this, it has been hypothesized that the disruption of the LC-NA system that occurs in AD could contribute to the chronic neuroinflammation and glial overactivation that lead to the pathogenesis and progression of AD. Therefore, restoration of noradrenergic signaling could represent a potential therapeutic strategy to reduce the progression of this disease...spadoctoral thesisopen access616.894-053.9(043.2)Enfermedad de AlzheimerAlzheimer's diseaseNeurociencias (Medicina)2490 Neurociencias