Percorrer por autor "Outeiro, Tiago Fleming"
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- Extracellular Alpha-Synuclein Oligomers Modulate Synaptic Transmission and Impair LTP Via NMDA-Receptor ActivationPublication . Diógenes, Maria José; Dias, Raquel B.; Rombo, Diogo M.; Miranda, Hugo Vicente; Maiolino, Francesca; Guerreiro, Patrícia; Näsström, Thomas; Franquelim, Henri G.; Oliveira, Luis M. A.; Castanho, Miguel A. R. B.; Lannfelt, Lars; Bergström, Joakim; Ingelsson, Martin; Quintas, Alexandre; Sebastião, Ana M.; Lopes, Luísa V.; Outeiro, Tiago FlemingParkinson’s disease (PD) is the most common representative of a group of disorders known as synucleinopathies, in which misfolding and aggregation of -synuclein (a-syn) in various brain regions is themajorpathological hallmark. Indeed, themotorsymptomsinPDare causedby a heterogeneous degeneration of brain neurons not only in substantia nigra pars compacta but also in other extrastriatal areas of the brain. In addition to the well known motor dysfunction in PD patients, cognitive deficits and memory impairment are also an important part of the disorder, probably due to disruption of synaptic transmission and plasticity in extrastriatal areas, including the hippocampus. Here, we investigated the impact of a-syn aggregation onAMPAandNMDAreceptor-mediated rat hippocampal (CA3-CA1) synaptic transmission and long-term potentiation (LTP), the neurophysiological basis for learning and memory. Our data show that prolonged exposure to a-syn oligomers, but not monomers or fibrils, increases basal synaptic transmission through NMDA receptor activation, triggering enhanced contribution of calcium-permeable AMPA receptors. Slices treated with a-syn oligomers were unable to respond with further potentiation to theta-burst stimulation, leading to impaired LTP. Prior delivery of a low-frequency train reinstated the ability to express LTP, implying that exposuretoa-synoligomersdrivestheincreaseofglutamatergicsynaptictransmission,preventingfurtherpotentiationbyphysiologicalstimuli. Our novel findings provide mechanistic insight on how a-syn oligomers may trigger neuronal dysfunction and toxicity in PD and other synucleinopathies.
- People with early onset Parkinson’s disease : empowered to improve carePublication . Domingos, Josefa; Bastos, Maria do Carmo Teixeira; Couto, Rui; Cameira, Ana Rita; Cardoso, Ana Leal; Reffóios, Alexandre; Magalhães, Susana; Massano, João; Outeiro, Tiago FlemingPatient organizations play an ever-growing role in modern societies by providing organized resources for patients and care partners. Importantly, patient organizations enable patients to define and share their needs and views. In Parkinson’s disease (PD), patient organizations play significant roles in different countries. However, there is limited support and resources tailored for people with early onset Parkinson’s disease (EOPD). These individuals face unique social, professional, and personal challenges that are often not accounted for by general PD organizations, which play very important roles for a significant proportion of individuals with PD. In Portugal, this was the situation until 2022, when Young Parkies Portugal (YPP) was founded to allow people with EOPD and various stakeholders to join forces to cover their specific needs. In this manuscript, we aim to share our experience in building an association for people with EOPD, reflecting on the reasons for this need, the activities developed thus far, challenges in implementation, and future directions. In summary, we believe that nonprofit organizations like YPP play an essential role in shaping the care and support of people with PD care and should be considered key partners of care alongside the larger multidisciplinary team. We are confident that sharing our experience can inspire and guide the implementation of similar initiatives in other countries.