Percorrer por autor "Silva, Rita Caridade"
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- Focused Neuroprotection in Parkinson's Disease: Effects of N-Acetylcysteine and MRI-guided Ultrasound NeuromodulationPublication . Silva, Rita Caridade; Araújo, B.; Vilaça-Ferreira, A. C.; Vilela, C.; Teixeira, C.; Martins-Macedo, J.; Soares-Guedes, C.; Gomes, Eduardo D.; Meriaux, S.; Larrat, B.; Wade-Martins, R.; Fernandes, H. J.; Teixeira, F.; Gomes, EduardoParkinson’s Disease (PD) is characterized by a progressive degeneration of dopaminergic neurons (DAn) in the brain, leading to severe symptomatology. Current treatments mainly address motor symptoms rather than preventing DAn damage or degeneration. Hence, there is an urgent need for novel strategies, particularly those that can combine neuroprotective and neuroregenerative approaches [1]. Drug repurposing is a powerful method for identifying new applications for approved drugs outside the scope of the original medical indication [2]. Under this concept, N-acetylcysteine (NAC), a potent antioxidant, has shown therapeutic abilities in modulating oxidative stress and preventing dopamine-induced cell death [3], suggesting potential disease-modifying actions in PD. Notably, recent data from our team revealed that NAC could restore dopamine transporter (DAT) levels in the dorsal striatum of PD animals [4].
- From the gut to the brain: Is microbiota a new paradigm in Parkinson’s disease treatment?Publication . Vilela, Cristiana; Araújo, Bruna; Guedes, Carla; Silva, Rita Caridade; Macedo, Joana Martins; Teixeira, Catarina; Gomes, Eduardo; Prudêncio, Cristina; Vieira, Mónica; Teixeira, Fábio G.Parkinson’s disease (PD) is recognized as the second most prevalent primary chronic neurodegenerative disorder of the central nervous system. Clinically, PD is characterized as a movement disorder, exhibiting an incidence and mortality rate that is increasing faster than any other neurological condition. In recent years, there has been a growing interest concerning the role of the gut microbiota in the etiology and pathophysiology of PD. The establishment of a brain–gut microbiota axis is now real, with evidence denoting a bidirectional communication between the brain and the gut microbiota through metabolic, immune, neuronal, and endocrine mechanisms and pathways. Among these, the vagus nerve represents the most direct form of communication between the brain and the gut. Given the potential interactions between bacteria and drugs, it has been observed that the therapies for PD can have an impact on the composition of the microbiota. Therefore, in the scope of the present review, we will discuss the current understanding of gut microbiota on PD and whether this may be a new paradigm for treating this devastating disease.
- Modulation of brain structure and motor function by safinamide multimodal actions in a pre-clinical model of Parkinson’s DiseasePublication . Araújo, Bruna; Campos, Jonas; Silva, Rita Caridade; Pinheiro, Bárbara Mendes; Marques, Raquel; Barata, Sandra; Lima, Rui; Macedo, Joana Martins; Gomes, Eduardo; Larrat, Benoit; Salgado, António; Mériaux, Sébastien; Domingues, Sofia; Teixeira, Fábio; Gomes, EduardoTo date, no neuroprotective/disease-modifying strategy has been approved as a Parkinson’s Disease (PD) therapy, because of the‘one-disease-one-target’ view that has been followed. New drug-based therapeutic routes, namely Safinamide, have been introduced as a promising multimodal drug combining dopaminergic and non-dopaminergic (neuroprotective) actions, representing a new potential alternative therapy to prevent or delay PD progression. Thus, the present work addressed Safinamide's impact on PD, relying on the possibility of potentiating dopaminergic neurons (DAn) survival by tackling cellular/molecular impairments responsible for its failure. Safinamide (10mg/kg) was given by oral gavage to a 6-OHDA pre-clinical rat model. DAn survival, neuroinflammation, and redox system homeostasis were assessed by histological and molecular analysis. Additionally, to overpass the selective blood-brain barrier (BBB) permeability, which reduces drug bioavailability reaching PD brain regions, we conducted magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) to transiently open the BBB to precisely deliver Safinamide in PD-affected areas. Results revealed that Safinamide monotherapy was able to potentiate the densities of DAn and fibers, revealing a protective effect when compared to the untreated group. To understand possible pathways associated with this improvement, we found that Safinamide appears to be a modulator of the antioxidant and autophagy systems since an increase in the expression levels of DJ-1, SOD-1, and LC3B was observed when compared to the non-treated group. Furthermore, Safinamide presents a potential modulatory activity on neuroinflammation and astrogliosis, as a decrease in microglia (CD11b+) and astrocytic (GFAP+) cells number was observed when compared to 6-OHDA group. Additionally, the anatomical and functional MRI analysis exhibited connectivity and metabolite alterations. Collectively, these data demonstrate the promising therapeutic potential of Safinamide as a neuroprotection strategy for PD, which may open new therapeutic opportunities for individuals in prodromal stages, potentially delaying clinical manifestation in high-risk patients.
