A5033413781- Sirtuins and Resveratrol in Medicine
- Parkinson's Disease Mechanisms and Treatments
- Adipose Tissue and Metabolism
- Biochemical effects in animals
- Alzheimer's disease research and treatments
- Extracellular vesicles in disease
- Cardiovascular Disease and Adiposity
- Genetic diversity and population structure
- Genetics, Aging, and Longevity in Model Organisms
- Calcium signaling and nucleotide metabolism
- Advanced Glycation End Products research
- Autophagy in Disease and Therapy
- Liver Disease Diagnosis and Treatment
- MicroRNA in disease regulation
- Wildlife Ecology and Conservation
- Diet, Metabolism, and Disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Syndromes and Imprinting
- Neurological Disease Mechanisms and Treatments
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Telomeres, Telomerase, and Senescence
- Genetic Neurodegenerative Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Phytochemicals and Antioxidant Activities
Universidade Nova de Lisboa
2017-2024
University of Lisbon
2010-2017
Universidade do Porto
2003-2014
Instituto de Medicina Molecular João Lobo Antunes
2010-2013
Universidade Estadual de Mato Grosso do Sul
2013
Massachusetts Institute of Technology
2003-2006
University of Helsinki
2003
Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. 2 was previously shown modulate proteotoxicity age-associated neurodegenerative disorders such as Alzheimer Parkinson disease (PD). However, the precise molecular mechanisms involved remain unclear. Here, we provide mechanistic insight into interplay between sirtuin α-synuclein, major component of pathognomonic protein inclusions in PD other synucleinopathies. We found that α-synuclein is...
α-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings cellular pathologies associated still elusive, complicating development effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational...
Sirtuin proteins are conserved regulators of aging that have recently emerged as important modifiers several diseases which commonly occur later in life, such cancer, diabetes, cardiovascular and neurodegenerative diseases. In mammals, there seven sirtuins (SIRT1-7), display diversity subcellular localization function. SIRT1 has received much attention due to its possible impact on longevity, while biological therapeutic roles other been underestimated just recognized. Here we focus SIRT2, a...
Background The simultaneous accumulation of different misfolded proteins in the central nervous system is a common feature many neurodegenerative diseases. In most cases, co-occurrence abnormal deposited observed brain regions and cell populations, but, some instances, can be found same cellular aggregates. Co-occurrence tau α-synuclein (α-syn) aggregates has been described disorders with primary deposition α-syn, such as Parkinson's disease dementia Lewy bodies. Although it known that α-syn...
Reactive oxygen species (ROS) such as superoxide radicals are responsible for the pathogenesis of various human diseases. ROS generated during normal metabolic process in all oxygen-utilizing organisms. The copper-zinc-containing SOD (SOD1) acts a major defense against by detoxifying anion. In model organisms, SOD1 has been shown to play role aging process. However, exact protein remains be resolved. We show that RNA interference (RNAi) induces senescence fibroblasts. This premature depends...
Insulin resistance is a major predictor of the development metabolic disorders. Sirtuins (SIRTs) have emerged as potential targets that can be manipulated to counteract age-related diseases, including type 2 diabetes. SIRT2 has been recently shown exert important effects, but whether regulates insulin sensitivity in hepatocytes currently unknown. The aim this study investigate possibility and elucidate underlying molecular mechanisms. Here, we show downregulated insulin-resistant livers, was...
Klotho has recently emerged as a regulator of aging. To investigate the role in regulation cellular senescence, we generated stable MRC‐5 human primary fibroblast cells knockdown for expression by RNAi. Downregulation dramatically induces premature senescence with concomitant upregulation p21. The p21 is associated cell cycle arrest at G1/S boundary. Knockdown p53 attenuated restores normal growth and replicative potential. These results demonstrate that normally regulates repressing p53/p21...
Parkinson's disease is characterized by the presence of cytoplasmic inclusions, known as Lewy bodies, containing both aggregated α-synuclein and its interaction partner, synphilin-1. While synphilin-1 to accelerate inclusion formation in mammalian cells, effect on cytotoxicity remains elusive.We expressed wild-type or R621C mutant either alone combination with yeast Saccharomyces cerevisiae monitored intracellular localization proteins well repercussions growth, oxidative stress cell death....
Abstract. Mitochondrial DNA variation was studied in the butterfly genus Phyciodes (Lepidoptera: Nymphalidae) by sequencing 1450 bp of COI gene from 140 individuals all eleven currently recognized species. The study focused on four species particular that have been taxonomically difficult for past century, P. tharos , cocyta batesii and pulchella . A cladistic analysis ninety‐eight unique haplotypes showed forms a monophyletic group with graphica as most basal Of three informal groups...
Worldwide we are facing a serious demographic challenge due to the dramatic growth of population over 60 years. It is expected that proportion this will nearly double from 12 22 %, between 2015 and 2050. This shift comes with major health socio-economic concerns. Nutrition fundamental determinant both disease its role in extending healthy lifespan object considerable research. Notably, malnutrition one main threats quality life among elderly. Therefore, knowledge about nutritional status...
Abstract α‐synuclein (α‐syn) is the major component of Lewy bodies, a pathological hallmark Parkinson's disease and other synucleinopathies. The characterization α‐syn post‐translational modifications (PTMs), thought to interfere with its aggregation propensity cellular signaling, has been limited by availability extraction methods endogenous protein from cells tissues, antibodies toward PTMs. Here, taking advantage thermostability, we applied method achieve high enrichment soluble both...
Mutations in the MPV17 gene are associated with hepatocerebral form of mitochondrial depletion syndrome. The mechanisms through which mutations cause respiratory chain dysfunction and mtDNA is still unclear. encodes an inner membrane protein that was recently described to function as a non-selective channel. Although its exact unknown, it thought be important maintenance potential (ΔΨm). To obtain more information about role human disease, we investigated effect knockdown selected known...
Extracellular vesicles (EVs) mediate communication in physiological and pathological conditions. In the pathogenesis of type 2 diabetes, inter-organ plays an important role its progress metabolic surgery leads to remission. Moreover, gut dysbiosis is emerging as a diabetogenic factor. However, it remains unclear how senses alterations whether this transmitted other tissues via EVs. Using diet-induced prediabetic mouse model, we observed that protein packaging gut-derived EVs (GDE),...
We investigated antioxidant capacity, phenolic content and phytotoxic effects in seven species of fruit native to Brazil: Acrocomia aculeata, Hymenaea stigonocarpa, Tamarindus indica, Byrsonima intermedia, Psidium firmum, Myrciaria cauliflora Ficus obtusifolia. Phytotoxic were assessed from crude ethanol extracts semipurified fractions. In four the fruits, total content, as determined by Folin-Ciocalteu assay, was higher peel than pulp. found that correlated significantly with capacity....
Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are agents physiological and pathological conditions, although they have been associated with obesity comorbidities, their protein cargo this context remains largely unknown. To decipher messages encapsulated EVs, we isolated plasma-derived EVs from a diet-induced obese murine model. Obese plasma exhibited decline diversity while...
Protein conformational disorders are associated with the appearance, persistence, accumulation, and misprocessing of aberrant proteins in cell. The etiology renal tubular dysgenesis (RTD) is linked to mutations angiotensin-converting enzyme (ACE). Here, we report identification a novel ACE mutation (Q1069R) an RTD patient. Q1069R found sequestered endoplasmic reticulum also subject increased proteasomal degradation, preventing its transport cell surface extracellular fluids. Modulation...