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Abstract(s)
A doença de Alzheimer (DA) é uma doença neurodegenerativa progressiva caracterizada por declínio cognitivo, perda de memória e alterações comportamentais. Apesar da extensa pesquisa, atualmente não há cura para a DA e a patogénese exata permanece desconhecida. Esta tese fornece uma revisão abrangente dos avanços recentes na compreensão e tratamento da DA, explorando os mecanismos moleculares subjacentes à DA, incluindo a formação de placas beta-amiloides, hiper fosforilação da proteína tau, neuroinflamação e o papel de fatores genéticos, como o alelo ε4 da APOE. Adicionalmente, são discutidas as mais recentes abordagens terapêuticas, abrangendo tratamentos farmacológicos recorrendo tanto a inibidores da acetilcolinesterase e antagonistas dos recetores NMDA, como a novas terapias, incluindo anticorpos monoclonais como o Aducanumab. Estratégias não farmacológicas, como intervenções dietéticas com ácidos gordos ómega-3, ómega- 6 e flavonoides, bem como o uso potencial de psicadélicos para aumentar a neuroplasticidade, também são temas abordados nesta monografia. Ao longo da tese destacam-se pesquisas emergentes sobre o papel dos microRNAs e RNAs circulares na patogénese da doença de Alzheimer, apresentando novos potenciais tratamentos para intervenções personalizadas ao utente. Esta monografia sublinha a complexidade da Doença de Alzheimer e evidenciada a necessidade de abordagens de tratamento multifacetadas para gerir e potencialmente mitigar a progressão desta doença debilitante.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioural changes. Despite extensive research, there is currently no cure for AD, and the exact pathogenesis remains elusive. This thesis provides a comprehensive review of recent advances in the understanding and treatment of AD. It explores the molecular mechanisms underlying AD, including amyloid-beta plaque formation, tau hyperphosphorylation, neuroinflammation, and the role of genetic factors such as the APOE ε4 allele. Additionally, the thesis discusses the latest therapeutic approaches, encompassing both pharmacological treatments, such as acetylcholinesterase inhibitors and NMDA receptor antagonists, and novel therapies including monoclonal antibodies like Aducanumab. Non-pharmacological strategies, such as dietary interventions with omega-3 fatty acids and flavonoids, as well as the potential use of psychedelics to enhance neuroplasticity, are also examined. Emerging research on the role of microRNAs and circular RNAs in AD pathogenesis is highlighted, presenting new avenues for targeted interventions. This thesis underscores the complexity of AD and emphasizes the need for multi-faceted treatment approaches to manage and potentially mitigate the progression of this debilitating disease.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioural changes. Despite extensive research, there is currently no cure for AD, and the exact pathogenesis remains elusive. This thesis provides a comprehensive review of recent advances in the understanding and treatment of AD. It explores the molecular mechanisms underlying AD, including amyloid-beta plaque formation, tau hyperphosphorylation, neuroinflammation, and the role of genetic factors such as the APOE ε4 allele. Additionally, the thesis discusses the latest therapeutic approaches, encompassing both pharmacological treatments, such as acetylcholinesterase inhibitors and NMDA receptor antagonists, and novel therapies including monoclonal antibodies like Aducanumab. Non-pharmacological strategies, such as dietary interventions with omega-3 fatty acids and flavonoids, as well as the potential use of psychedelics to enhance neuroplasticity, are also examined. Emerging research on the role of microRNAs and circular RNAs in AD pathogenesis is highlighted, presenting new avenues for targeted interventions. This thesis underscores the complexity of AD and emphasizes the need for multi-faceted treatment approaches to manage and potentially mitigate the progression of this debilitating disease.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2024, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Alzheimer's disease (AD) Neurodegeneration Amyloid-beta (Aβ) Tau hyperphosphorylation Neuroinflammation APOE ε4 Acetylcholinesterase inhibitors NMDA receptor antagonists Aducanumab Omega-3 Omega-6 Fatty acids Flavonoids Psychedelics Psychedelics MicroRNAs (miRNAs) Circular RNAs (circRNAs) Neuroplasticity Mestrado Integrado - 2024