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Neuropharmacology ; 174: 108118, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32380022

RESUMEN

Alzheimer's disease (AD) is an age-specific neurodegenerative disease that compromises cognitive functioning and impacts the quality of life of an individual. Pathologically, AD is characterised by abnormal accumulation of beta-amyloid (Aß) and hyperphosphorylated tau protein. Despite research advances over the last few decades, there is currently still no cure for AD. Although, medications are available to control some behavioural symptoms and slow the disease's progression, most prescribed medications are based on cholinesterase inhibitors. Over the last decade, there has been increased attention towards novel drugs, targeting alternative neurotransmitter pathways, particularly those targeting serotonergic (5-HT) system. In this review, we focused on 5-HT receptor (5-HTR) mediated signalling and drugs that target these receptors. These pathways regulate key proteins and kinases such as GSK-3 that are associated with abnormal levels of Aß and tau in AD. We then review computational studies related to 5-HT signalling pathways with the potential for providing deeper understanding of AD pathologies. In particular, we suggest that multiscale and multilevel modelling approaches could potentially provide new insights into AD mechanisms, and towards discovering novel 5-HTR based therapeutic targets.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Modelación Específica para el Paciente , Receptores de Serotonina/metabolismo , Serotoninérgicos/metabolismo , Serotoninérgicos/uso terapéutico , Animales , Humanos , Modelación Específica para el Paciente/tendencias , Resultado del Tratamiento
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