A5028262800- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Endoplasmic Reticulum Stress and Disease
- Signaling Pathways in Disease
- Mitochondrial Function and Pathology
- Prion Diseases and Protein Misfolding
- Medicinal Plants and Neuroprotection
- Autophagy in Disease and Therapy
- Biochemical effects in animals
- Adipose Tissue and Metabolism
- Amino Acid Enzymes and Metabolism
- Tuberous Sclerosis Complex Research
- Genetic Neurodegenerative Diseases
- Metabolomics and Mass Spectrometry Studies
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- ATP Synthase and ATPases Research
- RNA regulation and disease
- Neurological diseases and metabolism
- Cerebrovascular and genetic disorders
- Liver Disease Diagnosis and Treatment
- GABA and Rice Research
- Genetics and Neurodevelopmental Disorders
Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
2019-2024
IP
Abstract The pathogenesis of Alzheimer’s disease (AD), a slowly-developing age-related neurodegenerative disorder, is result the action multiple factors including deregulation Ca 2+ homeostasis, mitochondrial dysfunction, and dysproteostasis. Interaction these in astrocytes, principal homeostatic cells central nervous system, still poorly understood. Here we report that immortalized hippocampal astrocytes from 3xTg-AD mice (3Tg-iAstro cells) bioenergetics impaired, reduced glycolysis oxygen...
Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder characterized by the development of benign tumors in various organs, including brain, and often accompanied epilepsy, neurodevelopmental comorbidities intellectual disability autism. A key hallmark TSC hyperactivation mechanistic target rapamycin (mTOR) signaling pathway, which induces alterations cortical metabolic processes astrocytes, among other cellular functions. These changes could modulate seizure susceptibility,...
Abstract Deregulation of protein synthesis and ER stress/unfolded response (ER stress/UPR) have been reported in astrocytes. However, the relationships between deregulation stress/UPR, as well their role altered homeostatic support Alzheimer’s disease (AD) astrocytes remain poorly understood. Previously, we that astrocytic cell lines from 3xTg-AD mice (3Tg-iAstro) was impaired ER-mitochondria distance reduced. Here show 3Tg-iAstro is associated with an increase p-eIF2α downregulation GADD34....
Abstract Alzheimer’s disease (AD) is a progressive neurodegeneration with dysfunctions in both the ubiquitin–proteasome system (UPS) and autophagy. Astroglia participation AD an attractive topic of research, but molecular patterns are partially defined available vitro models have technical limitations. Immortalized astrocytes from hippocampus 3xTg-AD wild-type mice (3Tg-iAstro WT-iAstro, respectively) been obtained as attempt to overcome primary cell line limitations this study aims at...
Astrocytes perform important housekeeping functions in the nervous system including maintenance of adequate neuronal excitability, although regulatory mechanisms are currently poorly understood. The astrocytic Ca
In recent years, 4-phenylbutyric acid (4-PBA), an FDA-approved drug, has increasingly been used as a nonspecific chemical chaperone in vitro and vitro, but its pharmacodynamics is still not clear. this context, we developed validated Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) method to quantify 4-PBA NeuroBasal-A Dulbecco's Modified Eagle widely cell culture media. Samples were injected on Luna® 3 µm PFP(2) 100 Å (100 × 2.0 mm) column maintained at 40 °C. Water...
Alterations in the expression of glutamate/aspartate transporter (GLAST) have been associated with several neuropathological conditions including Alzheimer’s disease and epilepsy. However, mechanisms by which GLAST is altered are poorly understood. Here we used a combination pharmacological genetic approaches coupled quantitative PCR Western blot to investigate mechanism regulation Ca2+/calmodulin-activated phosphatase calcineurin (CaN). We show that treatment cultured hippocampal mouse...
Background/Objectives: Methyltransferase EZH2-mediated H3K27me3 is involved in liver inflammation and fibrosis, but its role hepatic metabolic derangements not yet clearly defined. We investigated if a high-fat diet (HFD) induced early changes EZH2 expression H3K27 me3 the of mice. Methods: Five-week-old mice were fed an HFD or low-fat (Control) for 2 weeks (2 W) 8 (8 W). Body weight was recorded weekly. Glycemia oral glucose tolerance assessed at baseline after W–8 W. Finally, livers...
Prion diseases arise from the conformational conversion of cellular prion protein (PrPC) into a self-replicating isoform (PrPSc). Although this process has been studied mostly in neurons, growing body evidence suggests that astrocytes express PrPC and are able to replicate accumulate PrPSc. Currently, remain incurable, while downregulation represents most promising therapy due reduction substrate for conversion. Here we show astrocyte-specific genetic ablation or pharmacological inhibition...
Alterations in the expression of glutamate/aspartate transporter (GLAST) have been associated with several neuropathological conditions including Alzheimer’s disease and epilepsy. However, mechanisms by which GLAST is altered are poorly understood. Here we used a combination pharmacological genetic approaches coupled quantitative PCR Western blot to investigate mechanism regulation Ca2+/calmodulin-activated phosphatase calcineurin (CaN). We show that treatment cultured hippocampal...
Abstract Alzheimer's disease (AD) represents an urgent yet unmet challenge for modern society, calling exploration of innovative targets and therapeutic approaches. Astrocytes, main homeostatic cells in the CNS, represent promising cell‐target. Our aim was to investigate if deletion regulatory CaNB1 subunit calcineurin astrocytes could mitigate AD‐related memory deficits, neuropathology, neuroinflammation. We have generated two, acute chronic, AD mouse models with astrocytic ablation...
ABSTRACT IP 3 receptor (IP R)-mediated Ca 2+ transfer at the mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) drives mitochondrial uptake and oxidative metabolism is linked to different pathologies, including Parkinson’s disease (PD). The dependence of efficiency on ER-mitochondria distance remains unexplored. Employing molecular rulers that stabilize ER-mitochondrial distances 5 nm resolution, using genetically-encoded indicators targeting ER lumen sub-mitochondrial...
ABSTRACT Deregulation of protein synthesis and ER stress/unfolded response (ER stress/UPR) have been reported in astrocytes. However, the relationships between deregulation stress/UPR, as well their role altered homeostatic support Alzheimer’s disease (AD) astrocytes remain poorly understood. Previously, we that astrocytic cell lines from 3xTg-AD mice (3Tg-iAstro) was impaired ER-mitochondria distance reduced. Here show 3Tg-iAstro is associated with an increase p-eIF2α downregulation GADD34....
ABSTRACT Astrocytes perform important housekeeping functions in the nervous system including maintenance of adequate neuronal excitability, although regulatory mechanisms are currently poorly understood. The astrocytic Ca 2+ /calmodulin-activated phosphatase calcineurin (CaN) is implicated development reactive gliosis and neuroinflammation, but its roles, control healthy brain unknown. We have generated a mouse line with conditional knockout (KO) CaN B1 (CaNB1) glial fibrillary acidic...
ABSTRACT In astrocytes, calcineurin (CaN) is involved in neuroinflammation and gliosis, while its role healthy CNS or early neuro-pathogenesis poorly understood. Here we report that astroglial CaN KO (ACN-KO) mice, at one month of age, proteome deranged hippocampus cerebellum. Bioinformatic analysis reveals association with Alzheimer’s disease (AD) epilepsy. We found significant overlap the an AD mouse model human subjects drug-resistant Barnes maze ACN-KO mice learned task but adopted...