DJ-1 as a deglycating enzyme: A unique function to explain a multifaceted protein?

The recently reported deglycating activity of DJ-1 reconciles several features previously described for the protein. The deglycating activity reported for DJ-1 may explain its different subcellular localizations, indeed the protein has been found in the cytoplasm, nucleus, and mitochondria. Moreover, this proposed activity could help to understand the involvement of the protein in Parkinson's disease (PD), tumor growth and diabetes

Family-specific scaling laws in bacterial genomes

Among several quantitative invariants found in evolutionary genomics, one of the most striking is the scaling of the overall abundance of proteins, or protein domains, sharing a specific functional annotation across genomes of given size. The size of these functional categories change, on average, as power-laws in the total number of protein-coding genes. Here, we show that such regularities are not restricted to the overall behavior of high-level functional categories, but also exist systematically at the level of single evolutionary families of protein domains. Specifically, the number of proteins within each family follows family-specific scaling laws with genome size. Functionally similar sets of families tend to follow similar scaling laws, but this is not always the case. To understand this systematically, we provide a comprehensive classification of families based on their scaling properties. Additionally, we develop a quantitative score for the heterogeneity of the scaling of families belonging to a given category or predefined group. Under the common reasonable assumption that selection is driven solely or mainly by biological function, these findings point to fine-tuned and interdependent functional roles of specific protein domains, beyond our current functional annotations. This analysis provides a deeper view on the links between evolutionary expansion of protein families and the functional constraints shaping the gene repertoire of bacterial genomes.Comment: 41 pages, 16 figure

Circadian Rhythm Abnormalities in Parkinson's Disease from Humans to Flies and Back

Clinical and research studies have suggested a link between Parkinson\u2019s disease (PD) and alterations in the circadian clock. Drosophila melanogaster may represent a useful model to study the relationship between the circadian clock and PD. Apart from the conservation of many genes, cellular mechanisms, signaling pathways, and neuronal processes, Drosophila shows an organized central nervous system and well-characterized complex behavioral phenotypes. In fact, Drosophila has been successfully used in the dissection of the circadian system and as a model for neurodegenerative disorders, including PD. Here, we describe the fly circadian and dopaminergic systems and report recent studies which indicate the presence of circadian abnormalities in some fly PD genetic models. We discuss the use of Drosophila to investigate whether, in adults, the disruption of the circadian system might be causative of brain neurodegeneration. We also consider approaches using Drosophila, which might provide new information on the link between PD and the circadian clock. As a corollary, since PD develops its symptomatology over a large part of the organism\u2019s lifespan and given the relatively short lifespan of fruit flies, we suggest that genetic models of PD could be used to perform lifelong screens for drug-modulators of general and/or circadian-related PD traits

Zipf and Heaps laws from dependency structures in component systems

Complex natural and technological systems can be considered, on a coarse-grained level, as assemblies of elementary components: for example, genomes as sets of genes, or texts as sets of words. On one hand, the joint occurrence of components emerges from architectural and specific constraints in such systems. On the other hand, general regularities may unify different systems, such as the broadly studied Zipf and Heaps laws, respectively concerning the distribution of component frequencies and their number as a function of system size. Dependency structures (i.e., directed networks encoding the dependency relations between the components in a system) were proposed recently as a possible organizing principles underlying some of the regularities observed. However, the consequences of this assumption were explored only in binary component systems, where solely the presence or absence of components is considered, and multiple copies of the same component are not allowed. Here, we consider a simple model that generates, from a given ensemble of dependency structures, a statistical ensemble of sets of components, allowing for components to appear with any multiplicity. Our model is a minimal extension that is memoryless, and therefore accessible to analytical calculations. A mean-field analytical approach (analogous to the "Zipfian ensemble" in the linguistics literature) captures the relevant laws describing the component statistics as we show by comparison with numerical computations. In particular, we recover a power-law Zipf rank plot, with a set of core components, and a Heaps law displaying three consecutive regimes (linear, sub-linear and saturating) that we characterize quantitatively

Antioxidant Therapy in Parkinson's Disease: Insights From Drosophila melanogaster

Reactive oxygen species (ROS) play an important role as endogenous mediators in several cellular signalling pathways. However, at high concentrations they can also exert deleterious effects by reacting with many macromolecules including DNA, proteins and lipids. The precise balance between ROS production and their removal via numerous enzymatic and nonenzymatic molecules is of fundamental importance for cell survival. Accordingly, many neurodegenerative disorders, including Parkinson\u2019s disease (PD), are associated with excessive levels of ROS, which induce oxidative damage. With the aim of coping with the progression of PD, antioxidant compounds are currently receiving increasing attention as potential co-adjuvant molecules in the treatment of these diseases, and many studies have been performed to evaluate the purported protective effects of several antioxidant molecules. In the present review, we present and discuss the relevance of the use of Drosophila melanogaster as an animal model with which to evaluate the therapeutic potential of natural and synthetic antioxidants. The conservation of most of the PD-related genes between humans and D. melanogaster, along with the animal\u2019s rapid life cycle and the versatility of genetic tools, makes fruit flies an ideal experimental system for rapid screening of antioxidant-based treatments

Antioxidant Therapy in Parkinson's Disease: Insights from Drosophila melanogaster.

Reactive oxygen species (ROS) play an important role as endogenous mediators in several cellular signalling pathways. However, at high concentrations they can also exert deleterious effects by reacting with many macromolecules including DNA, proteins and lipids. The precise balance between ROS production and their removal via numerous enzymatic and nonenzymatic molecules is of fundamental importance for cell survival. Accordingly, many neurodegenerative disorders, including Parkinson's disease (PD), are associated with excessive levels of ROS, which induce oxidative damage. With the aim of coping with the progression of PD, antioxidant compounds are currently receiving increasing attention as potential co-adjuvant molecules in the treatment of these diseases, and many studies have been performed to evaluate the purported protective effects of several antioxidant molecules. In the present review, we present and discuss the relevance of the use of Drosophila melanogaster as an animal model with which to evaluate the therapeutic potential of natural and synthetic antioxidants. The conservation of most of the PD-related genes between humans and D. melanogaster, along with the animal's rapid life cycle and the versatility of genetic tools, makes fruit flies an ideal experimental system for rapid screening of antioxidant-based treatments

DJ-1: A promising therapeutic candidate for ischemia-reperfusion injury.

DJ-1 is a multifaceted protein with pleiotropic functions that has been implicated in multiple diseases, ranging from neurodegeneration to cancer and ischemia-reperfusion injury. Ischemia is a complex pathological state arising when tissues and organs do not receive adequate levels of oxygen and nutrients. When the blood flow is restored, significant damage occurs over and above that of ischemia alone and is termed ischemia-reperfusion injury. Despite great efforts in the scientific community to ameliorate this pathology, its complex nature has rendered it challenging to obtain satisfactory treatments that translate to the clinic. In this review, we will describe the recent findings on the participation of the protein DJ-1 in the pathophysiology of ischemia-reperfusion injury, firstly introducing the features and functions of DJ-1 and, successively highlighting the therapeutic potential of the protein

Tea e neuroplasticidade: Identificação e intervenção precoce / Asd and neuroplasticity: Identification and early intervention

Este artigo apresenta um estudo sobre o Transtorno do Espectro Autista (TEA) e a importância da intervenção precoce nos primeiros meses e primeiros anos de vida. Destaca a neuroplasticidade cerebral enquanto avanço da ciência para a amenização dos sintomas, recuperando as habilidades por meio da formação de novas rotas sinápticas. Ao narrar que a intervenção precoce é significativa para a criança com TEA, conduz a refletir se as pessoas que trabalham neste campo estão capacitadas para entender o funcionamento cerebral dessas crianças por manifestarem no comportamento estereotipias, isolamento social e prejuízos de interação dificultado pelo mal uso da linguagem. A constatação destas reflexões caminha em adequar posturas para entender o papel do mediador ao propor estratégias de intervenção e da sua atuação para lidar com as crianças comprometidas, pois toda intervenção acontece dentro de um contexto social e interativo

Cisto de Baker e trombose venosa profunda: um diagnóstico diferencial. relato de caso/ Baker’s cyst and deep vein thrombosis: a differential diagnosis.case report

O Cisto de Baker, ou cisto poplíteo, apresenta-se como um aumento de volume na região posterior do joelho e se localiza entre a cabeça medial do músculo gastrocnêmio e o tendão do semimembranoso. Em adultos, há associação destes cistos com lesões intra-articulares, como as lesões meniscais, osteoartrite, artrite reumatóide e gota.As muitas semelhanças entre os sinais e sintomas do cisto de Baker e da Trombose Venosa Profunda (TVP) fizeram com que a primeira hipótese diagnóstica do caso fosse a TVP, uma doença cardiovascular relativamente frequente, cuja queixa clássica do paciente é a presença de edema e dor no membro inferior que, dependendo do local e extensão do trombo pode envolver a perna ou todo o membro.O objetivo deste estudo é abordar as características clínicas do Cisto de Baker e exames de imagem, demonstrando a evolução do paciente e o diagnóstico diferencial com Trombose Venosa Profunda

Superoxide Radical Dismutation as New Therapeutic Strategy in Parkinson's Disease.

Aging is the biggest risk factor for developing many neurodegenerative disorders, including idiopathic Parkinson's disease (PD). PD is still an incurable disorder and the available medications are mainly directed to the treatment of symptoms in order to improve the quality of life. Oxidative injury has been identified as one of the principal factors involved in the progression of PD and several indications are now reported in the literature highlighting the prominent role of the superoxide radical in inducing neuronal toxicity. It follows that superoxide anions represent potential cellular targets for new drugs offering a novel therapeutic approach to cope with the progression of the disease. In this review we first present a comprehensive overview of the most common cellular reactive oxygen and nitrogen species, describing their cellular sources, their potential physiological roles in cell signalling pathways and the mechanisms through which they could contribute to the oxidative damage. We then analyse the potential therapeutic use of SOD-mimetic molecules, which can selectively remove superoxide radicals in a catalytic way, focusing on the classes of molecules that have therapeutically exploitable properties.This work was supported by a grant from the Italian Ministry of Education, University and Research (2015T778JW)