Anti-diabetic drug pioglitazone reduces Islet amyloid aggregation overload in the Drosophila neuronal cells.

Amyloid-proteinopathy is observed in type 2 diabetes, where Islet amyloid polypeptide is secreted atypically and impedes cellular homeostasis. The thiazolidinediones family is reported to influence amyloid-beta aggregations. However, research on drug-based stimulation of insulin signaling to alleviate Islet amyloid aggregations is lacking.

Impaired insulin signaling and diet-induced type 3 diabetes pathophysiology increase amyloid β expression in the Drosophila model of Alzheimer's disease.

Compelling evidence has strongly linked unregulated sugar levels to developing Alzheimer's disease, suggesting Alzheimer's to be 'diabetes of the brain or 'type 3 diabetes. Insulin resistance contributes to the pathogenesis of Alzheimer's disease due to uncontrolled and unchecked blood glucose, though the interrelatedness between Alzheimer's disease and type 2 diabetes is debatable. Here we describe the consequences of inducing type 3 diabetes by feeding Drosophila on a high sucrose diet, which effectively mimics the pathophysiology of diabetes.

Disrupted nuclear import of cell cycle proteins in Huntington's/PolyQ disease causes neurodevelopment defects in cellular and Drosophila model.

Huntington's disease is caused by an expansion of CAG repeats in exon 1 of the huntingtin gene encoding an extended PolyQ tract within the Huntingtin protein (mHtt). This expansion results in selective degeneration of striatal medium spiny projection neurons in the basal ganglia. The mutation causes abnormalities during neurodevelopment in human and mouse models.

Expanded polyQ aggregates interact with sarco-endoplasmic reticulum calcium ATPase and Drosophila inhibitor of apoptosis protein1 to regulate polyQ mediated neurodegeneration in Drosophila.

Polyglutamine (polyQ) induced neurodegeneration is one of the leading causes of progressive neurodegenerative disorders characterized clinically by deteriorating movement defects, psychiatric disability, and dementia. Calcium [Ca] homeostasis, which is essential for the functioning of neuronal cells, is disrupted under these pathological conditions. In this paper, we simulated Huntington's disease phenotype in the neuronal cells of the Drosophila eye and identified [Ca] pump, sarco-endoplasmic reticulum calcium ATPase (SERCA), as one of the genetic modifiers of the neurodegenerative phenotype.

Hsc70-4 aggravates PolyQ-mediated neurodegeneration by modulating NF-κB mediated immune response in .

Huntington's disease occurs when the stretch of CAG repeats in exon 1 of the () gene crosses the permissible limit, causing the mutated protein (mHtt) to form insoluble aggregates or inclusion bodies. These aggregates are non-typically associated with various essential proteins in the cells, thus disrupting cellular homeostasis. The cells try to bring back normalcy by synthesizing evolutionary conserved cellular chaperones, and Hsp70 is one of the families of heat shock proteins that has a significant part in this, which comprises of heat-inducible and cognate forms.

Ayurvedic formulations Guduchi and Madhuyashti triggers JNK signaling mediated immune response and adversely affects Huntington phenotype.

Background: Huntington's disease manifests due to abnormal CAG trinucleotide expansion, in the first exon of the Huntingtin gene and disease progression involves genetic, immune, and environmental components. The pathogenesis is characterized by the formation of Inclusion Bodies, disruption of neuronal circuitry, cellular machinery, and apoptosis, resulting in gradual and progressive loss of neuronal cells, ultimately leading to nervous system dysfunction. Thus, the present study was conducted to assess the effect of two Ayurvedic formulations, Guduchi and Madhuyashti, on Huntington's phenotype, using Drosophila as a model system.

Nonapoptotic role of caspase-3 in regulating Rho1GTPase-mediated morphogenesis of epithelial tubes of Drosophila renal system.

Background: Cells trigger caspase-mediated apoptosis to eliminate themselves from the system when tissue needs to be sculptured, or they detect any abnormality within them, thus preventing irreparable damage to the host. However, nonapoptotic activities of caspases are also involved in many cellular functions. Interestingly, Drosophila Malpighian tubules (MTs) express apoptotic proteins, without succumbing to cell death.

Transcriptome profiling identifies multistep regulation through E93, Forkhead and Ecdysone Oxidase in survival of Malpighian tubules during metamorphosis in Drosophila.

Drosophila metamorphosis is associated with substantial metabolic activity involving cell death and cell proliferation leading to differentiation of adult tissues and structures. Unlike other larval tissues, Malpighian tubules (MTs) exhibit apoptotic immunity and do not undergo cell death but are carried over to the adult with some cell reorganisation. They persist despite the fact that they express apoptotic proteins and caspases.

A Forward Genetic Approach to Mapping a -Element Second Site Mutation Identifies as a Novel Tumor Suppressor in .

The use of transposons to create mutations has been the cornerstone of genetics in the past few decades. Second-site mutations caused by transpositions are often devoid of transposons and thereby affect subsequent analyses. In a -element mutagenesis screen, a second site mutation was identified on chromosome 3, wherein the homozygous mutants exhibit classic hallmarks of tumor suppressor mutants, including brain tumor and lethality; hence the mutant line was initially named as [].

Correction to: Molecular basis for efficacy of Guduchi and Madhuyashti feeding on different environmental stressors in Drosophila.

It has come to authors' attention that an inadvertent mistake was made in the construction of Figure 4 and Figure 6 of the original publication.

Molecular basis for efficacy of Guduchi and Madhuyashti feeding on different environmental stressors in Drosophila.

Stressors of different kinds adversely affect life history parameters like growth, development, and reproduction. Organisms overcome the negative impact of environmental stressors and strive to reach a tolerant state through genetic and metabolic activities. Ayurvedic formulations are reported to have life trait benefitting properties which improve capacity to withstand stress and tolerate adverse conditions.

Complex effects of Ayurvedic formulation: and on different components of life history may elude the elixir effect.

Formulations from the traditional Indian medicine, Ayurveda, have long been considered to have potent life-style enhancing effects, possibly by their effect(s) on key life-history attributes. Although several studies have reported beneficial effects of these formulations on different components of life history, few have investigated their concurrent influence on various life-history traits. Here, we report the results of an investigation showing the effect of two well-known Ayurvedic formulations, and , on fecundity and longevity of .

Drosophila Malpighian Tubules: A Model for Understanding Kidney Development, Function, and Disease.

The Malpighian tubules of insects are structurally simple but functionally important organs, and their integrity is important for the normal excretory process. They are functional analogs of human kidneys which are important physiological organs as they maintain water and electrolyte balance in the blood and simultaneously help the body to get rid of waste and toxic products after various metabolic activities. In addition, it receives early indications of insults to the body such as immune challenge and other toxic components and is essential for sustaining life.

Yorkie Regulates Neurodegeneration Through Canonical Pathway and Innate Immune Response.

Expansion of CAG repeats in certain genes has long been known to be associated with neurodegenerastion, but the quest to identity the underlying mechanisms is still on. Here, we analyzed the role of Yorkie, the coactivator of the Hippo pathway, and provide evidence to state that it is a robust genetic modifier of polyglutamine (PolyQ)-mediated neurodegeneration. Yorkie reduces the pathogenicity of inclusion bodies in the cell by activating cyclin E and bantam, rather than by preventing apoptosis through DIAP1.

Expression of polyQ aggregates in Malpighian tubules leads to degeneration in Drosophila melanogaster.

Background: Polyglutamine (polyQ) disorders are caused by expanded CAG (Glutamine) repeats in neurons in the brain. The expanded repeats are also expressed in the non-neuronal cells, however, their contribution to disease pathogenesis is not very well studied. In the present study, we have expressed a stretch of 127 Glutamine repeats in Malpighian tubules (MTs) of Drosophila melanogaster as these tissues do not undergo ecdysone induced histolysis during larval to pupal transition at metamorphosis.

Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster.

In insects, humoral response to injury is accomplished by the production of antimicrobial peptides (AMPs) which are secreted in the hemolymph to eliminate the pathogen. Drosophila Malpighian tubules (MTs), however, are unique immune organs that show constitutive expression of AMPs even in unchallenged conditions and the onset of immune response is developmental stage dependent. Earlier reports have shown ecdysone positively regulates immune response after pathogenic challenge however, a robust response requires prior potentiation by the hormone.

Molecular and genetic basis of depression.

Joyousness or sadness is normal reaction to state of life. If any of these lead to certain semi-permanent changes in daily life, then it is termed as mental disorder. Depression is one of the mental disorders with a state of low mood and aversion to activities that exerts a negative effect on a person's thoughts and behaviour.

Ecdysone regulates morphogenesis and function of Malpighian tubules in Drosophila melanogaster through EcR-B2 isoform.

Malpighian tubules are the osmoregulatory and detoxifying organs of Drosophila and its proper development is critical for the survival of the organism. They are made up of two major cell types, the ectodermal principal cells and mesodermal stellate cells. The principal and stellate cells are structurally and physiologically distinct from each other, but coordinate together for production of isotonic fluid.

Epithelial immune response in Drosophila malpighian tubules: interplay between Diap2 and ion channels.

Systemic immune response via the Immune deficiency pathway requires Drosophila inhibitor of apoptosis protein 2 to activate the NF-κB transcription factor Relish. Malpighian tubules (MTs), simple epithelial tissue, are the primary excretory organs, performing additional role in providing protection to Drosophila against pathogenic infections. MTs hold a strategic position in Drosophila as one of the larval tissues that are carried over to adults, unlike other larval tissues that are histolysed during pupation.

Neurodegeneration caused by polyglutamine expansion is regulated by P-glycoprotein in Drosophila melanogaster.

Trinucleotide CAG repeat disorders are caused by expansion of polyglutamine (polyQ) domains in certain proteins leading to fatal neurodegenerative disorders and are characterized by accumulation of inclusion bodies in the neurons. Clearance of these inclusion bodies holds the key to improve the disease phenotypes, which affects basic cellular processes such as transcription, protein degradation and cell signaling. In the present study, we show that P-glycoprotein (P-gp), originally identified as a causative agent of multidrug-resistant cancer cells, plays an important role in ameliorating the disease phenotype.

Immune response and anti-microbial peptides expression in Malpighian tubules of Drosophila melanogaster is under developmental regulation.

Malpighian tubules (MT) of Drosophila melanogaster are osmoregulatory organs that maintain the ionic balance and remove toxic substances from the body. Additionally they act as autonomous immune sensing organs, which secrete antimicrobial peptides in response to invading microbial pathogens. We show that the antimicrobial peptides (AMP) diptericin, cecropinA, drosocin and attacinA are constitutively expressed and are regulated in developmental stage specific manner.

Non-apoptotic function of apoptotic proteins in the development of Malpighian tubules of Drosophila melanogaster.

Drosophila metamorphosis is characterized by the histolysis of larval structures by programmed cell death, which paves the way for the establishment of adult-specific structures under the influence of the steroid hormone ecdysone. Malpighian tubules function as an excretory system and are one of the larval structures that are not destroyed during metamorphosis and are carried over to adulthood. The pupal Malpighian tubules evade destruction in spite of expressing apoptotic proteins, Reaper, Hid, Grim, Dronc and Drice.

Differential localization and processing of apoptotic proteins in Malpighian tubules of Drosophila during metamorphosis.

Drosophila development proceeds through three larval stages, before it pupates to reach adulthood. During pupation, larval tissues are destructed by programmed cell death and replaced by adult structures. Programmed cell death is a tightly regulated process accomplished by the induction of three closely linked pro-apoptotic genes reaper, hid and grim, ultimately leading to the activation of caspases, DRONC and DRICE and results in cell death.

Ecdysone signaling is required for proper organization and fluid secretion of stellate cells in the Malpighian tubules of Drosophila melanogaster.

Drosophila development is a tightly regulated process involving metamorphosis of a relatively less mobile larva to a highly motile adult, triggered by secretion of 20-hydroxyecdysone. Under the influence of ecdysone, most of the larval tissues degenerate, while the imaginal cells differentiate and form adult specific structures. Although the larval Malpighian tubules do not seem to be affected by ecdysone during metamorphosis, we show that ecdysone signaling plays an important role in the early development and functioning of Malpighian tubules.