Publications by authors named "Sara Pagnotta"

Jaundice is a common presentation of malaria, which arises from the accumulation of circulating bilirubin. It is not understood whether it represents an adaptive or maladaptive response to spp. infection.

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Whether jaundice, a common presentation of ( .) malaria (1-3) arising from the accumulation of circulating bilirubin, represents an adaptive or maladaptive response to spp. infection is not understood (1-3).

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Article Synopsis
  • Brain insulin resistance connects energy metabolism failure to cognitive decline in type 2 diabetes and Alzheimer's disease, but the early changes leading to insulin resistance are not well understood.
  • Abnormal levels of biliverdin reductase-A (BVR-A) are found in both conditions, linked to insulin resistance and affecting insulin signaling and energy production in the brain.
  • The study reveals that lower BVR-A disrupts insulin response and mitochondrial function, highlighting its importance for potential therapeutic targets to combat brain insulin resistance and neurodegeneration.
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Background: Paediatric Huntington disease with highly expanded mutations (HE-PHD; >80 CAG repeats) presents atypically, compared to adult-onset Huntington disease (AOHD), with neurodevelopmental delay, epilepsy, abnormal brain glucose metabolism, early striatal damage, and reduced lifespan. Since genetic GLUT-1 deficiency syndrome shows a symptom spectrum similar to HE-PHD, we investigated the potential role of the two main glucose transporters, GLUT-1 and GLUT-3, in HE-PHD.

Methods: We compared GLUT-1 and GLUT-3 protein expression in HE-PHD, juvenile-onset (JOHD), and AOHD brains (n = 2; n = 3; n = 6) and periphery (n = 3; n = 2; n = 2) versus healthy adult controls (n = 6; n = 6).

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Article Synopsis
  • Down syndrome is linked to Alzheimer's disease and involves early brain insulin resistance, which our previous research identified in children with DS before AD symptoms appear.
  • We tested the KYCCSRK peptide in Ts2Cje mice, finding it boosts insulin signaling, enhances mitochondrial function, and lowers oxidative stress.
  • The peptide also reduces levels of proteins associated with Alzheimer's and restores brain health by improving synaptic plasticity, offering potential new treatments for intellectual disability and AD in those with DS.
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The cells possess several mechanisms to counteract the over-production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), including enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Moreover, an important sensor involved in the anti-oxidant response is KEAP1-NRF2-ARE signaling complex. Under oxidative stress (OS), the transcription factor NRF2 can dissociate from the KEAP1-complex in the cytosol and translocate into the nucleus to promote the transcriptional activation of anti-oxidant genes, such as heme oxygenase 1 and NADPH quinone oxidoreductase.

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Aim: Biliverdin reductase-A (BVR-A) other than its canonical role in the degradation pathway of heme as partner of heme oxygenase-1 (HO1), has recently drawn attention as a protein with pleiotropic functions involved in insulin-glucose homeostasis. However, whether BVR-A expression is altered in type 2 diabetes (T2D) has never been evaluated.

Main Methods: BVR-A protein levels were evaluated in T2D (n = 44) and non-T2D (n = 29) subjects, who underwent complete clinical workup and routine biochemistry.

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Article Synopsis
  • Protein O-GlcNAcylation is a post-translational modification related to nutrition, linked to neurodegenerative diseases like Alzheimer's disease by disrupting glucose metabolism, which affects proteins like tau and APP.
  • Individuals with Down syndrome show early Alzheimer's symptoms and share similar pathological features, yet the relationship between O-GlcNAcylation and Down syndrome has not been studied before this research.
  • The study reveals that altered mechanisms regulating OGT and OGA disrupt O-GlcNAcylation in the Down syndrome brain and suggests that inhibiting OGA could have neuroprotective effects by restoring O-GlcNAcylation and reducing Alzheimer's-related markers.
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Down syndrome (DS) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans, which results from the triplication of chromosome 21. To search for biomarkers for the early detection and exploration of the disease mechanisms, here, we investigated the protein expression signature of peripheral blood mononuclear cells (PBMCs) in DS children compared with healthy donors (HD) by using an in-depth label-free shotgun proteomics approach. Identified proteins are found associated with metabolic pathways, cellular trafficking, DNA structure, stress response, cytoskeleton network, and signaling pathways.

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Down syndrome (DS) is the most common genetic cause of intellectual disability that is associated with an increased risk to develop early-onset Alzheimer-like dementia (AD). The brain neuropathological features include alteration of redox homeostasis, mitochondrial deficits, inflammation, accumulation of both amyloid beta-peptide oligomers and senile plaques, as well as aggregated hyperphosphorylated tau protein-containing neurofibrillary tangles, among others. It is worth mentioning that some of the triplicated genes encoded are likely to cause increased oxidative stress (OS) conditions that are also associated with reduced cellular responses.

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Trehalose solutions were investigated by means of broadband dielectric spectroscopy at different water contents, ranging from an anhydrous sample to w(C) = 40%. While the structural α-relaxation was detectable only in the low hydration and dry samples, and in a quite limited range of temperatures, two secondary processes were presented and characterized in all the solutions investigated. In particular, the fastest secondary process displayed a characteristic behavior widely observed in other small organic glass formers.

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Studies of liquid water in its supercooled region have helped us better understand the structure and behavior of water. Bulk water freezes at its homogeneous nucleation temperature (approximately 235 K), but protein hydration water avoids this crystallization because each water molecule binds to a protein. Here, we study the dynamics of the hydrogen bond (HB) network of a percolating layer of water molecules and compare the measurements of a hydrated globular protein with the results of a coarse-grained model that successfully reproduces the properties of hydration water.

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The reliability of tripeptide glutathione as an excellent model for protein-water interactions is tested by means of broadband dielectric spectroscopy. Measurements performed on aqueous solutions with different water contents show a surprisingly rich relaxation map that strongly resembles those observed for more complex protein macromolecules. At variance with what is normally observed for solutions of hydrophilic compounds with similar molecular weights, the presence of at least two water-related processes is detected.

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Sol-gel technique represents a remarkably versatile method for protein encapsulation. To enhance sol-gel biocompatibility, systems envisaging the presence of calcium and phosphates in the sol-gel composition were recently prepared and investigated. Unfortunately, the low pH at which solutions were prepared (pH < 2.

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Conventional ion-sensitive microelectrodes cannot be used in small cells, since they create too large an electrical leak at the site of penetration. Membrane potentials can be measured in such cells with the whole-cell configuration of the patch-clamp technique, after obtaining a high-resistance seal (giga-seal) to the cell membrane. Achieving such seals with patch-type microelectrodes silanized and filled with ion-sensitive cocktails has proved very difficult.

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The function of GABA or glycine during early postnatal development remains controversial as their action is reported as either excitatory or inhibitory. The present study addressed the question of the functional role of GABA or glycine on rat motoneurons shortly after birth. For this purpose, using in vitro preparations from immature rats (postnatal age, P0-P4 days), we recorded from lumbar spinal motoneurons and hypoglossal motoneurons.

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