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Investigating the neuroprotective effect of plant (poly)phenols in models of Parkinson´s disease
Publication . Macedo, Diana
Parkinson’s disease (PD) is the second most common neurodegenerative disease,
and affects 1-2% of the population worldwide after the age of 65 years. Currently, there are
only symptomatic treatment for PD and these do not mitigate the underlying causes of the
disease.(...)
(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis
Publication . Macedo, Diana; Jardim, Carolina; Figueira, Inês; Almeida, A. Filipa; McDougall, Gordon J.; Stewart, Derek; Yuste, Jose E.; Tomás-Barberán, Francisco A.; Tenreiro, Sandra; Outeiro, Tiago F.; Santos, Cláudia N.; Instituto de Tecnologia Química e Biológica António Xavier (ITQB); NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Centro de Estudos de Doenças Crónicas (CEDOC); Nature Publishing Group
Parkinson's disease (PD) is an age-related neurodegenerative disease associated with the misfolding and aggregation of alpha-synuclein (aSyn). The molecular underpinnings of PD are still obscure, but nutrition may play an important role in the prevention, onset, and disease progression. Dietary (poly)phenols revert and prevent age-related cognitive decline and neurodegeneration in model systems. However, only limited attempts were made to evaluate the impact of digestion on the bioactivities of (poly)phenols and determine their mechanisms of action. This constitutes a challenge for the development of (poly)phenol-based nutritional therapies. Here, we subjected (poly)phenols from Arbutus unedo to in vitro digestion and tested the products in cell models of PD based on the cytotoxicity of aSyn. The (poly)phenol-digested metabolites from A. unedo leaves (LPDMs) effectively counteracted aSyn and H2O2 toxicity in yeast and human cells, improving viability by reducing aSyn aggregation and inducing its clearance. In addition, LPDMs modulated pathways associated with aSyn toxicity, such as oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial impairment, and SIR2 expression. Overall, LPDMs reduced aSyn toxicity, enhanced the efficiency of ER-associated protein degradation by the proteasome and autophagy, and reduced oxidative stress. In total, our study opens novel avenues for the exploitation of (poly)phenols in nutrition and health.
From the baker to the bedside: yeast models of Parkinson's disease
Publication . Menezes, R.; Macedo, Diana Leonor Constantino; Santos, Claudia N.; Tenreiro, Sandra; Outeiro, Tiago F; Instituto de Tecnologia Química e Biológica António Xavier (ITQB); NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Centro de Estudos de Doenças Crónicas (CEDOC); Shared Science Publishers
The baker’s yeast Saccharomyces cerevisiae has been extensively explored for our understanding of fundamental cell biology processes highly conserved in the eukaryotic kingdom. In this context, they have proven invaluable in the study of complex mechanisms such as those involved in a variety of human disorders. Here, we first provide a brief historical perspective on the emergence of yeast as an experimental model and on how the field evolved to exploit the potential of the model for tackling the intricacies of various human diseases. In particular, we focus on existing yeast models of the molecular underpinnings of Parkinson’s disease (PD), focusing primarily on the central role of protein quality control systems. Finally, we compile and discuss the major discoveries derived from these studies, highlighting their far-reaching impact on the elucidation of PD-associated mechanisms as well as in the identification of candidate therapeutic targets and compounds with therapeutic potential.
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Fundação para a Ciência e a Tecnologia
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SFRH
Número da atribuição
SFRH/BD/73429/2010