A5088657522- Advanced Glycation End Products research
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Biochemical effects in animals
- Protein Structure and Dynamics
- Neuropeptides and Animal Physiology
- Enzyme Structure and Function
- Natural Antidiabetic Agents Studies
- Spine and Intervertebral Disc Pathology
- Scoliosis diagnosis and treatment
- Prion Diseases and Protein Misfolding
- Trace Elements in Health
- Metabolism and Genetic Disorders
- Genetic Neurodegenerative Diseases
- Free Radicals and Antioxidants
- Chemical Reaction Mechanisms
- Alcohol Consumption and Health Effects
- Glycosylation and Glycoproteins Research
- Metal complexes synthesis and properties
- Musculoskeletal pain and rehabilitation
- Lipid Membrane Structure and Behavior
- Phytase and its Applications
- Biochemical and biochemical processes
- Nerve Injury and Rehabilitation
- Anesthesia and Pain Management
Health Research Institute of the Balearic Islands
2017-2024
Research Institute of Health Sciences
2014-2024
Universitat de les Illes Balears
2015-2024
Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
2015-2024
Servei de Salut de les Illes Balears
2009-2022
Vall d'Hebron Hospital Universitari
2016-2020
Fundació Universitat-Empresa de les Illes Balears
2020
Hospital Universitario Son Espases
2017
Clinica Rotger
2015
Hospital de l'Esperança
2009
Abstract The formation of a heterogeneous set advanced glycation end products (AGEs) is the final outcome non-enzymatic process that occurs in vivo on long-life biomolecules. This process, known as glycation, starts with reaction between reducing sugars, or their autoxidation products, amino groups proteins, DNA, lipids, thus gaining relevance under hyperglycemic conditions. Once AGEs are formed, they might affect biological function biomacromolecule and, therefore, induce development...
Intrinsically disordered proteins (IDPs) are not well described by a single 3D conformation but an ensemble of them, which makes their structural characterization especially challenging, both experimentally and computationally. Most all-atom force fields designed for folded give too compact IDP conformations. α-Synuclein is well-known because its relation to Parkinson's disease (PD). To understand role in this at the molecular level, efficient methodology needed generation conformational...
Aggregation and misfolding of the prion protein (PrP) are thought to be cause a family lethal neurodegenerative diseases affecting humans other animals. Although structures PrP from several species have been solved, still little is known about mechanisms that lead misfolded species. Here, we show region comprising hairpin formed by helices H2 H3 stable independently folded unit able retain its secondary tertiary structure also in absence rest sequence. We prove isolated H2H3 highly...
Protein glycation causes loss-of-function through a process that has been associated with several diabetic-related diseases. Additionally, hypothesized as promoter of protein aggregation, which could explain the observed link between hyperglycaemia and development aggregating Despite its relevance in range diseases, mechanism induces aggregation remains unknown. Here we describe molecular basis how is linked to by applying variety complementary techniques study nonenzymatic hen lysozyme...
Understanding the factors that determine protein stability is interesting because it directly reflects evolutionary pressure coming from function and environment. Here, we have combined experimental computational methods to study of IscU, a bacterial scaffold highly conserved in most organisms an essential component iron-sulfur cluster biogenesis pathway. We demonstrate effect zinc its consequence strongly depend on sample history. IscU marginally stable at low ionic strength point undergoes...
Abstract Myo-inositol hexaphosphate (phytate; IP6) is a natural compound that abundant in cereals, legumes, and nuts it has the ability to chelate metal cations. The binding of IP6 transition metals suggests could be used for treatment metal-catalyzed protein glycation, which appears trigger diabetes-related diseases. Our vitro studies showed reduced formation Fe 3+ -catalyzed advanced glycation end-products (AGEs). This led us perform randomized cross-over trial investigate impact daily...
Pyridoxamine, one of the natural forms vitamin B6, is known to be an effective inhibitor formation advanced glycation end products (AGEs), which are closely related various human diseases. Pyridoxamine stable complexes with metal ions that catalyze oxidative reactions taking place in stages protein cascade. It also reacts reactive carbonyl compounds generated as byproducts glycation, thereby preventing further damage. We applied Density Functional Theory study primary antioxidant activity...
Myo-inositol-1,2,3,4,5,6-hexakisphosphate (IP6), commonly found in plant-derived foods, has important pharmacological properties against many pathological processes. One of them could be the neurodegeneration, stimulated by a dysregulated metal metabolism. Consequently, we explore here role IP6 mitigating neurodegenerative processes catalyzed free iron. Using dopamine and ascorbic acid as models neuronal redox systems, demonstrate that effectively chelates Fe³⁺, inhibiting its ability to...
A comprehensive theoretical study based on density functional theory calculations (B3LYP and M06−2X functionals) of the formation Schiff bases pyridoxamine analogues with two different aldehydes was conducted. The reaction mechanism found to involve steps, namely: (1) a carbinolamine (2) dehydration give final imine. Also, consistent available experimental evidence, rate-determining step process determined by means functional. Using an appropriate solvation method reactant conformation...
Abstract Parkinson’s disease (PD) is one of the most prevalent neurodegenerative disorders affecting worldwide population. One its hallmarks intraneuronal accumulation insoluble Lewy bodies (LBs), which cause death dopaminergic neurons. α-Synuclein (αS) main component these LBs and in them, it commonly contains non-enzymatic post-translational modifications, such as those resulting from reaction with reactive carbonyl species arising side products glycolysis (mainly methylglyoxal)....
All globular proteins undergo transitions from their native to unfolded states if exposed either cold or heat perturbation. While the heat-induced transition is well described for a large number of proteins, in media compatible with natural environments, limited examples denatured concern artificially destabilized, instance, by presence denaturants, ad hoc point mutations, both. Here, we provide characterization low temperature state Yfh1, protein that undergoes denaturation around water...
The origins of C-H activation in pyridoxal-5'-phosphate (PLP) Schiff bases and modulation reaction specificity PLP-enzymes are still not completely understood. There no available studies that compare the reactivity C4' carbons ketimine with Cα their aldimine counterparts, which is essential to unravel mechanisms govern evolution common carbanionic intermediates. Second-order rate constants for phosphate-catalyzed proton/deuterium exchange reactions D(2)O suffer a 10(5)-fold increase due base...
Prion diseases are characterized by conformational changes of a cellular prion protein (PrP(C)) into β-sheet-enriched and aggregated conformer (PrP(Sc)). Shadoo (Sho), member the family, is expressed in central nervous system (CNS) highly conserved among vertebrates. On basis histoanatomical colocalization sequence similarities, it suspected that Sho PrP may be functionally related. The downregulation expression during pathology direct interaction between PrP, as revealed two-hybrid...
Abstract Protein aggregation with the concomitant formation of amyloid fibrils is related to several neurodegenerative diseases, but also non-neuropathic amyloidogenic diseases and non-neurophatic systemic amyloidosis. Lysozyme protein involved in latter it widely used as a model system study mechanisms underlying fibril its inhibition. Several phenolic compounds have been reported inhibitors formation. However, anti-aggregating capacity other heteroaromatic has not studied any depth. We...
We study the effect of an advanced glycation end product (<italic>N</italic>(ε)-(carboxyethyl)lysine), found on Lewy bodies people suffering from Parkinson’s disease, conformational and aggregation features alpha-synuclein.
Intraneuronal aggregation of the intrinsically disordered protein α-synuclein is at core Parkinson's disease and related neurodegenerative disorders. Several reports show that concentration salts in medium heavily affects its rate fibril morphology, but a characterization individual monomeric conformations underlying these effects still lacking. In this work, we have applied our α-synuclein-optimized coarse-grained molecular dynamics approach to decipher structural features monomer under...
Abstract Pyridoxamine has been found to inhibit protein glycation and avoid the formation of advanced end‐products (AGEs). One mechanisms by which pyridoxamine can involves scavenger carbonyl groups with capacity. In this work, we conducted a kinetic study reactions various carbohydrates under physiological pH temperature. The involving hexoses were give tricyclic compound ( 5 ) in addition pyridoxal pyridoxine. Such inhibits Amadori rearrangement other compounds glycating properties....
Human α-synuclein is a small monomeric protein (140 residues) essential to maintain the function of dopaminergic neurons and neuronal redox balance. However, it holds dark side since able clump inside forming insoluble aggregates known as Lewy bodies, which are considered hallmark Parkinson's disease. Sporadic mutations nonenzymatic post-translational modifications well-known stimulate formation bodies. Yet, effect on has been studied less intense. Therefore, here we study how nitration...