Percorrer por autor "Outeiro, Tiago"
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- Documentos das provas de agregação de Tiago Fleming de Oliveira Outeiro. Titulo da Lição: Desenovelamento e agregação de proteínas em biologia e em doençaPublication . Outeiro, TiagoNos termos do Art. 5º, alínea b, Decreto de Lei nº 239/2007 de 19 de junho e Art. 4º do Regulamento de Atribuição do Título Académico de Agregado da Universidade do Algarve, o presente documento corresponde ao relatório da Unidade Curricular Bases Moleculares de Neurodegeneração (BMN), no âmbito da prestação de Provas de Agregação em Ciências Biomédicas. Esta unidade foi desenhada para ser incluída no plano de estudos do Mestrado em Ciências Biomédicas – Mecanismos de Doenças (ver Anexo), acreditado pela Agência de Avaliação e Acreditação do Ensino Superior (A3Es) (Processo ACEF/PERA 2021/22). Uma primeira secção contextualiza os objetivos e conteúdos da unidade curricular proposta, no âmbito das doenças neurodegenerativas. Segue-se uma secção onde é efetuado o enquadramento da unidade curricular no plano de estudos do Mestrado em Ciências Biomédicas – Mecanismos de Doenças, e onde é detalhada também a implementação desta unidade curricular. A quarta secção descreve o programa da unidade curricular, os objetivos de aprendizagem e os conteúdos programáticos a abordar. As secções finais detalham o método de avaliação proposto e a bibliografia recomendada para a unidade curricular. A apresentação da presente proposta decorre da experiência do proponente, adquirida pela regência e lecionação da unidade curricular “Bases Moleculares de Neurodegeneração” (BMN) integrada na Licenciatura em Ciências Biomédicas. A proposta decorre ainda da experiência em ensino adquirida pelo proponente ao longo de mais de 20 anos, enquanto docente em diversos cursos avançados de Mestrado e Doutoramento em diversas Universidades nacionais e internacionais, e em Escolas de Verão organizadas pelo proponente ou em que o proponente participou como docente convidado. A disciplina aqui proposta está alinhada com o objectivo do Mestrado em Ciências Biomédicas para preparar profissionais capazes de relatar, perante uma audiência os progressos científicos mais recentes nas diversas áreas de investigação biomédica fundamental ou aplicada, e de desenvolverem uma apreciação crítica e informada desses progressos através da participação em palestras e da leitura de artigos publicados nas áreas relevantes.
- Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregationPublication . Fricke, Michel; Mechel, Anna; Evers, Lennart; Twellsieck, Björn; Grein, Jessica M.; Cima-Omori, Maria-Sol; Al-Azzani, Mohammed; Outeiro, Tiago; Zweckstetter, Markus; Holzbaur, Erika L.F.; Boecker, C. AlexanderParkinson disease (PD)-associated mutations in the LRRK2 gene hyperactivate LRRK2 kinase activity, leading to increased phosphorylation of a subset of RAB GTPases, which are master regulators of intracellular trafficking. In neurons, processive retrograde transport of autophagosomes is essential for autophagosome maturation and effective degradation of autophagosomal cargo in the axon. Here, we show that knockout of the LRRK2-counteracting RAB phosphatase PPM1H causes a gene-dose-dependent disruption of the axonal transport of autophagosomes, leading to impaired degradation of axonal alpha-synuclein (aSyn), a key protein in PD pathophysiology. Defective autophagosome transport and impaired aSyn degradation correlate with increased aSyn aggregation in primary PPM1H knockout neurons exposed to preformed fibrils of aSyn, an effect that is dependent on LRRK2 kinase activity. These findings mechanistically link LRRK2- mediated RAB hyperphosphorylation to defective autophagosomal degradation and enhanced aggregation of aSyn, positioning the LRRK2-RAB axis as a key driver of PD pathophysiology.
- Lewy bodies are not associated with neuronal or synaptic loss in dementia with lewy bodiesPublication . Hawksworth, Jade I.; Kirkby‐Geddes, Eddie; Thom, Searlait; O'Neill, Joe; Ikwue, Amelia; Wood, Lucy; Outeiro, Tiago; Erskine, DanielAims: The misfolding and accumulation of the protein α-synuclein (αSyn) into cytoplasmic inclusions termed Lewy bodies (LBs) and Lewy neurites is the defining neuropathological feature of LB diseases, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The loss of neurons and/or synapses has been postulated to underlie the clinical syndrome of DLB. The present study sought to elucidate the relationship between LB burden and neuronal and synaptic loss in DLB. Methods: Post-mortem brain tissue from the cingulate gyrus and inferior temporal gyrus, two regions vulnerable to LB pathology, was obtained from DLB (N=20) and control cases (N=20). Formalin-fixed paraffin-embedded tissue was stained to quantify LB, Alzheimer-type pathology and a neuronal marker. Frozen tissue from the contralateral hemisphere was processed for immunoblotting to compare the abundance of synaptic markers across cases. Results: Across both regions, no evidence of reduced total neuronal density was observed, but a modest reduction in parvalbumin interneurons was observed in the cingulate gyrus, and there were only modest reductions in some synaptic markers in DLB. LB burden was markedly variable across DLB cases but was not associated with any synaptic marker abundance or neuronal density. Conclusions: Taken together, these findings do not support an association between LB density and neuronal or synaptic loss in DLB, even in regions with particularly high burdens of LBs, such as the cingulate gyrus. These findings suggest that the link between αSyn proteinopathy and disease requires further investigation.
- Neuroimaging and pathology biomarkers in parkinson’s disease and parkinsonismPublication . Cilia, Roberto; Arnaldi, Dario; Ballanger, Bénédicte; Ceravolo, Roberto; Micco, Rosa De; Del Sole, Angelo; Eleopra, Roberto; Endo, Hironobu; Fasano, Alfonso; Hoenig, Merle C.; Horsager, Jacob; Lehéricy, Stéphane; Leta, Valentina; Moda, Fabio; Nolano, Maria; Outeiro, Tiago; Parkkinen, Laura; Pavese, Nicola; Quattrone, Andrea; Ray, Nicola J.; Reich, Martin M.; Rektorová, Irena; Strafella, Antonio P.; Tagliavini, Fabrizio; Tessitore, Alessandro; van Eimeren, ThiloThe “Neuroimaging and Pathology Biomarkers in Parkinson’s Disease” course held on 12–13 September 2025 in Milan, Italy, convened an international faculty to review state-ofthe- art biomarkers spanning neurotransmitter dysfunction, protein pathology and clinical translation. Here, we synthesize the four themed sessions and highlights convergent messages for diagnosis, stratification and trial design. The first session focused on neuroimaging markers of neurotransmitter dysfunction, highlighting how positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) provided complementary insights into dopaminergic, noradrenergic, cholinergic and serotonergic dysfunction. The second session addressed in vivo imaging of protein pathology, presenting recent advances in PET ligands targeting α- synuclein, progress in four-repeat tau imaging for progressive supranuclear palsy and corticobasal syndromes, and the prognostic relevance of amyloid imaging in the context of mixed pathologies. Imaging of neuroinflammation captures inflammatory processes in vivo and helps study pathophysiological effects. The third session bridged pathology and disease mechanisms, covering the biology of α-synuclein and emerging therapeutic strategies, the clinical potential of seed amplification assays and skin biopsy, the impact of co-pathologies on disease expression, and the “brain-first” versus “body-first” model of pathological spread. Finally, the fourth session addressed disease progression and clinical translation, focusing on imaging predictors of phenoconversion from prodromal to clinically overt stages of synucleinopathies, concepts of neural reserve and compensation, imaging correlates of cognitive impairment, and MRI approaches for atypical parkinsonism. Biomarker-informed pharmacological, infusion-based, and surgical strategies, including network-guided and adaptive deep brain stimulation, were discussed as examples of how multimodal biomarkers may inform personalized management. Across all sessions, the need for harmonization, longitudinal validation, and pathology-confirmed outcome measures was consistently emphasized as essential for advancing biomarker qualification in multicentre research and clinical practice.