Publicação
Synaptic plasticity in Alzheimer's disease : role of amyloid β and therapies
| Resumo: | Background: Alzheimer’s Disease (AD) is a neurodegenerative disorder with no available effective treatment yet. Synaptic dysfunction and synaptic loss is likely to be the primary cause of cognitive impairment in AD. Therefore, understanding the signaling pathways underlying amyloid β (Aβ)-mediated synaptotoxicity represents a significant tool to develop better AD therapies. The aim of this review is to elucidate physiological pathways involved in synaptic plasticity, and explore the role of Aβ and recent therapeutic strategies for AD in synaptic plasticity. Methods: The bibliographic sources used were Pubmed and Google, restricting to the period 2000-2013, with some exceptions when relevant to the review. Results: Aβ oligomers activate glutamate NMDA receptors triggering influx of calcium and excitotoxicity. Excessive NMDA receptor activation subsequently causes reactive endocytosis of postsynaptic membrane receptors, associated to LTD and loss of dendritic spines. Further excitatory network activation may be associated to Aβ-induced GABAergic neurotransmission impairment. Tauroursodeoxycholic acid, a potential AD therapeutic strategy, has been demonstrated to reduce Aβ production, preserve dendritic spines by modulating PSD-95, and may present GABAergic properties thanks to its taurine moiety. Conclusion: Up to date, several mechanisms responsible for synaptic plasticity and synaptic loss in AD have been unveiled allowing to a better understanding of AD pathogenesis and development of new promising AD therapeutic compounds. |
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| Autores principais: | Ribeiro, Maria Filipe C. M. O. |
| Assunto: | Aβ oligomers AMPA receptor; APP processing NMDA receptor Synaptic plasticity TUDCA Mestrado Integrado - 2013 |
| Ano: | 2013 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Background: Alzheimer’s Disease (AD) is a neurodegenerative disorder with no available effective treatment yet. Synaptic dysfunction and synaptic loss is likely to be the primary cause of cognitive impairment in AD. Therefore, understanding the signaling pathways underlying amyloid β (Aβ)-mediated synaptotoxicity represents a significant tool to develop better AD therapies. The aim of this review is to elucidate physiological pathways involved in synaptic plasticity, and explore the role of Aβ and recent therapeutic strategies for AD in synaptic plasticity. Methods: The bibliographic sources used were Pubmed and Google, restricting to the period 2000-2013, with some exceptions when relevant to the review. Results: Aβ oligomers activate glutamate NMDA receptors triggering influx of calcium and excitotoxicity. Excessive NMDA receptor activation subsequently causes reactive endocytosis of postsynaptic membrane receptors, associated to LTD and loss of dendritic spines. Further excitatory network activation may be associated to Aβ-induced GABAergic neurotransmission impairment. Tauroursodeoxycholic acid, a potential AD therapeutic strategy, has been demonstrated to reduce Aβ production, preserve dendritic spines by modulating PSD-95, and may present GABAergic properties thanks to its taurine moiety. Conclusion: Up to date, several mechanisms responsible for synaptic plasticity and synaptic loss in AD have been unveiled allowing to a better understanding of AD pathogenesis and development of new promising AD therapeutic compounds. |
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