Pathophysiological regulation of the production, aggregation and toxicity of the amyloid beta-peptide in Alzheimer's disease

Society increase in live expectancy will cause a rise in Alzheimer’s Disease (AD) diagnosis, thus, there is a need to further understand how it works. One of the main culprits of this disease amyloid-β peptide (Aβ), this protein has a physiological function as monomers. But, once starts to aggregate...

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Detalles Bibliográficos
Autor: Picón Pagès, Pol
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/675512
Acceso en línea:http://hdl.handle.net/10803/675512
Access Level:acceso abierto
Palabra clave:Alzheimer’s Disease
Amyloid-beta peptide
Calcium
Oxidative stress
Malaltia d’Alzheimer
Proteïna beta amiloide
Calci
Estrès oxidatiu
616.8
Descripción
Sumario:Society increase in live expectancy will cause a rise in Alzheimer’s Disease (AD) diagnosis, thus, there is a need to further understand how it works. One of the main culprits of this disease amyloid-β peptide (Aβ), this protein has a physiological function as monomers. But, once starts to aggregate, Aβ becomes neurotoxic. In this thesis, I have demonstrated a novel physiological function of monomeric Aβ as inductor of insulin receptor signalling, while its oligomers block the same signalling. I have described a neurotoxic feedback loop between oligomeric Aβ and an increase in BACE1 presence. I have studied novel calcium regulators in the development of the disease. I showed a novel pathway that links Aβ as a blocker of LTP. Finally, I have characterised the region of interaction of albumin c-terminus with Aβ and its neuroprotective effect.