Proteomic Mapping of Proline-rich oligopeptide 7a Induced Neuroprotection in a Zebrafish Parkinson’s Model
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ABSTRACT:
ORGANISM(S): Danio Rerio
SUBMITTER: Emidio Beraldo Neto
PROVIDER: PXD061139 | JPOST Repository | Tue Feb 25 00:00:00 GMT 2025
REPOSITORIES: jPOST
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Project description:Ayurvedic drug formulations Bacopa monnieri and Centella asiatica are known to have neuroprotective effects. These have been traditionally used in the treatment of Alzhemeir’s disease, and other neurological deficits. Using pan neuronal Aβ42 model of Drosophila melanogaster, a mass spectrometry based quantitative proteomic analysis platform was used to generate the data on proteins altered in response to the Aβ42 toxicity and restoration of altered proteins by consumption of aqueous extracts of two Ayurvedic drug formulations Bacopa monnieri and Centella asiatica aqueous extract. Quantitative proteomic analysis resulted in 0.67 million mass spectra corresponding to 2,59,168 peptide-spectrum matches (PSM) mapping to 24,305 non- redundant peptides corresponding to 11,480 Drosophila melanogaster proteins. Proteins were filtered for >3 PSMs, resulting in 9,540 proteins. Flies expressing Aβ42 significantly altered 517 proteins which were involved in maintaining essential neuronal functions. Supplementing flies with Bacopa monnieri or Centella asiatica extract commonly rescued 224 proteins from Aβ42 toxicity, moreover, extract supplemented group significantly altered proteins which were additionally supporting neuronal maintenance in flies with Aβ42 stress.
2021-11-25 | PXD027101 | Pride
Project description:Early molecular events related to cytoskeleton are poorly described in Amyotrophic Lateral Sclerosis (ALS), especially in the Schwann cell (SC), which offers strong trophic support to motor neurons. DAVID tool identified cytoskeleton-related genes by employing the Cellular Component of Gene Ontology (CCO) in a large gene profiling of lumbar spinal cord and sciatic nerve of presymptomatic SOD1G93A mice. One and five CCO terms related to cytoskeleton were described from the spinal cord deregulated genes of 40 days (actin cytoskeleton) and 80 days (microtubule cytoskeleton, cytoskeleton part, actin cytoskeleton, neurofilament cytoskeleton and cytoskeleton) old transgene mice, respectively. Also, four terms were depicted from the deregulated genes of sciatic nerve of 60 days old transgenes (actin cytoskeleton, cytoskeleton part, microtubule cytoskeleton and cytoskeleton). Kif1b was the unique gene that appeared deregulated in more than one studied region or presymptomatic age. The expression of Kif1b (qPCR) elevated in the lumbar spinal cord (40 days old) and decreased in the sciatic nerve (60 days old) of presymptomatic ALS mice, results that were in line to microarray findings. Upregulation (24.8 fold) of Kif1b was seen in laser microdissected enriched immunolabeled motor neurons from the spinal cord of 40 days old presymptomatic SOD1G93A mice. Furthermore, Kif1b was downregulated in the sciatic nerve Schwann cells of presymptomatic ALS mice (60 days old) that were enriched by means of cell microdissection (6.35 fold), cell sorting (3.53 fold) and primary culture (2.70 fold) technologies. The gene regulation of cytoskeleton molecules is an important occurrence in motor neurons and Schwann cells in presymptomatic stages of ALS and may be relevant in the dying back mechanisms of neuronal death. Differential regulation of Kif1b in the spinal cord and sciatic nerve cells emerged as key event in ALS. Sciatic nerve from SOD1G93A and Non transgenic controls from 60 days were used in the experiments. 4 biological replicates were used. A reference sample, comprised by RNA from different neonatal organs (heart, liver, kidney) were used in the hybridations
2014-04-22 | E-GEOD-56926 | biostudies-arrayexpress
Project description:SEL1L-HRD1 endoplasmic reticulum-associated degradation (ERAD) is essential for protein folding quality control and maintaining homeostasis in the ER. Defects in SEL1L-HRD1 ERAD complex has been linked to early onset of severe neurological syndromes. However, its physiological importance and underlying mechanisms in neurons remain poorly understood. This study established a mouse model with neuron-specific deletion of Sel1L and revealed that neuronal SEL1L-HRD1 ERAD is essential for maintaining one-carbon metabolism, motor function, and overall viability.
2026-02-10 | GSE299894 | GEO
Project description:Early molecular events related to cytoskeleton are poorly described in Amyotrophic Lateral Sclerosis (ALS), especially in the Schwann cell (SC), which offers strong trophic support to motor neurons. DAVID tool identified cytoskeleton-related genes by employing the Cellular Component of Gene Ontology (CCO) in a large gene profiling of lumbar spinal cord and sciatic nerve of presymptomatic SOD1G93A mice. One and five CCO terms related to cytoskeleton were described from the spinal cord deregulated genes of 40 days (actin cytoskeleton) and 80 days (microtubule cytoskeleton, cytoskeleton part, actin cytoskeleton, neurofilament cytoskeleton and cytoskeleton) old transgene mice, respectively. Also, four terms were depicted from the deregulated genes of sciatic nerve of 60 days old transgenes (actin cytoskeleton, cytoskeleton part, microtubule cytoskeleton and cytoskeleton). Kif1b was the unique gene that appeared deregulated in more than one studied region or presymptomatic age. The expression of Kif1b (qPCR) elevated in the lumbar spinal cord (40 days old) and decreased in the sciatic nerve (60 days old) of presymptomatic ALS mice, results that were in line to microarray findings. Upregulation (24.8 fold) of Kif1b was seen in laser microdissected enriched immunolabeled motor neurons from the spinal cord of 40 days old presymptomatic SOD1G93A mice. Furthermore, Kif1b was downregulated in the sciatic nerve Schwann cells of presymptomatic ALS mice (60 days old) that were enriched by means of cell microdissection (6.35 fold), cell sorting (3.53 fold) and primary culture (2.70 fold) technologies. The gene regulation of cytoskeleton molecules is an important occurrence in motor neurons and Schwann cells in presymptomatic stages of ALS and may be relevant in the dying back mechanisms of neuronal death. Differential regulation of Kif1b in the spinal cord and sciatic nerve cells emerged as key event in ALS.
2014-04-22 | GSE56926 | GEO
Project description:Dominantly inherited expanded repeat neurodegenerative diseases are typically caused by the expansion of existing variable copy number tandem repeat sequences in otherwise unrelated genes. Repeats located in translated regions encode polyglutamine that is thought to be the toxic agent, however in several instances the expanded repeat is in an untranslated region, necessitating multiple pathogenic pathways or an alternative common toxic agent. As numerous clinical features are shared by several of these diseases, and expanded repeat RNA is a common intermediary, RNA has been proposed as a common pathogenic agent. Various forms of repeat RNA are toxic in animal models, by multiple distinct pathways. In Drosophila, repeat-containing double-stranded RNA (rCAG.rCUG~100) toxicity is dependent on Dicer processing evident with the presence of single-stranded rCAG7, which have been detected in affected HD brains. Microarray analysis of Drosophila rCAG.rCUG~100 repeat RNA toxicity revealed perturbation of several pathways including innate immunity. Recent reports of elevated circulating cytokines prior to clinical onset, and age-dependent increased inflammatory signaling and microglia activation in the brain, suggest that immune activation precedes neuronal toxicity. Since the Toll pathway is activated by certain forms of RNA, we assessed the role of this pathway in RNA toxicity. We find that rCAG.rCUG~100 activates Toll signaling and that RNA toxicity is dependent on this pathway. The sensitivity of RNA toxicity to autophagy further implicates innate immune activation. Expression of rCAG.rCUG~100 was therefore directed in glial cells and found to be sufficient to cause neuronal dysfunction. Non-autonomous toxicity due to expanded repeat-containing double-stranded RNA mediated activation of innate immunity is therefore proposed as a candidate pathway for this group of human genetic diseases. The heads from newly eclosed male Drosophila were used for RNA extraction and profiling on Affymetrix Drosophile Genome 2.0 microarrays. Nine samples were analysed, representing control and experimental lines. Two independent lines of rCAG.rCUG~100 double-stranded RNA were analysed in triplicate. These were compared to 4xUAS control analysed in triplicate. All transgenes were expressed using the elavII-GAL4 pan-neuronal driver. Candidates were selected from the pool of transcripts which showed a 'present' call in all samples. T-tests were performed on raw values to determine samples that showed a significant difference with a P-value < 0.05.
2013-04-05 | E-GEOD-42910 | biostudies-arrayexpress
Project description:Bioprinting holds the promise to revolutionize therapeutic development and healthcare; however, we still lack an in-depth understanding of how cells respond to stress experienced during the bioprinting process. Here, we assess at the molecular and cellular level the effects of bioprinting-induced stress on cell morphology, metabolism, and behavior using human umbilical vein endothelial cells. We demonstrate that mild preconditioning of the stress response in cells using heat shock before bioprinting helps cells to rapidly respond to bioprinting-associated stress, mitigating negative effects. We hypothesize this is in part mediated by the small heat shock protein 27 (Hsp27) which is known to play a role in stabilizing actin in the cytoskeleton. This results in restoration of cellular viability, morphology, metabolism, and function, including vascularization. Our study outlines an easy-to-implement strategy to improve cell viability following bioprinting, facilitating the real-life application of bioprinting.
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2020-07-29 | GSE148985 | GEO
Project description:Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. In mammals, the pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin F2α (PGF2α) are known to be involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH has not been established. Here we show that Lh induces PGF2α synthesis through its stimulation of Tnfα production in trout, a primitive teleost fish. Importantly, trout recombinant Tnfα (rTnfα) and PGF2α recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfα secretion or PG synthesis and those of rTnfα are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfαâdependent increase in PGF2α production is necessary for the pro-ovulatory actions of Lh in a teleost fish. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility. Preovulatory follicles from brook trout from four different females (n = 4) were isolated and incubated in the absence or presence of salmon LH. Total RNA of control and LH-treated preovulatory follicles from each of the four females was analyzed.
2015-12-31 | E-GEOD-67592 | biostudies-arrayexpress
Project description:Effective toxicological testing of the vast number of new and existing chemicals currently in use will require efficient and cost effective methods. We evaluated the utility of a simple, low cost toxicity testing system employing the nematode Caenorhabditis elegans to identify toxicologically relevant changes in gene expression. Dichlorvos and fenamiphos, which are organophosphorous pesticides that inhibit acetylcholinesterase were chosen as model toxicants to test the usefulness of the C. elegans toxicity testing system, and mefloquine, which appears to perturb neuronal Ca++ homeostasis, provided an out-group for analysis. Keywords: gene expression array-based (RNA / in situ oligonucleotide)
2009-06-03 | GSE12298 | GEO
Project description:Early-life inflammation increases the risk for mental disorders in later life by altering the long-term neuronal spine engulfment capacity of microglia. This process involves a bidirectional, tightly regulated interaction between the nervous and immune systems. However, the mechanisms whereby local immune responses modulate microglial cells are not fully understood. Here we define a critical role of microglial IL-27–IL-27Rα signaling in improving depressive symptoms induced by postnatal immune activation (PIA). IL-27 suppresses excessive microglial phagocytic activity, preserving synaptic density and preventing synaptic loss. Mechanistically, IL-27 activates STAT1 phosphorylation and nuclear translocation, inducing Trem2 expression—a key regulator of microglial phagocytosis—thus restoring synaptic stability. Genetic or pharmacological inhibition of Trem2 abolishes the antidepressant effects of IL-27, confirming the functional importance of this axis. These findings uncover a previously unrecognized IL-27–STAT1–Trem2 signaling axis regulating microglial function and synaptic integrity. Notably, IL-27 treatment also ameliorates behavioral deficits in a prenatal stress (PNS) model, underscoring its broader relevance across early-life adversity paradigms. Toxicological and immunological assessments demonstrate that IL-27 administration is well tolerated, with no significant adverse effects, supporting its translational viability. Together, these results position IL-27 as a promising immunotherapeutic candidate and drug target for mood disorders associated with neurodevelopmental immune dysregulation.
2026-03-28 | GSE298652 | GEO