Secretomic effects of amyloid beta peptides on Alzheimer’s disease related proteins in differentiated SH-SY5Y neuroblastoma cell
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: Teerakul Arpornsuwan
PROVIDER: PXD045244 | JPOST Repository | Wed Jan 03 00:00:00 GMT 2024
REPOSITORIES: jPOST
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| DMEM+RA+BDNF-1.mgf | Mgf | |||
| DMEM+RA+BDNF-1.mzXML | Mzxml | |||
| DMEM+RA+BDNF-2.mgf | Mgf | |||
| DMEM+RA+BDNF-2.mzXML | Mzxml | |||
| DMEM+RA+BDNF-3.mzXML | Mzxml |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Exercise has emerged as a powerful variable that can improve cognitive function and delay age-associated cognitive decline and Alzheimer’s disease (AD), however, the underlying mechanisms are poorly understood. To determine if protective mechanisms may occur at the transcriptional level, we used microarrays to investigate the relationship between physical activity levels and gene expression patterns in the cognitively-intact aged human hippocampus. In parallel, hippocampal gene expression patterns associated with Aging and AD were assessed using publicly available microarray data profiling hippocampus from young (20-59 yrs), cognitively-intact aging (73-95 yrs) and age-matched AD cases. To identify “anti-Aging/AD” transcription patterns associated with physical activity, probesets significantly associated with both physical activity and Aging/AD were identified and their directions of expression change in each condition were compared. Remarkably, of the 2138 probesets significant in both datasets, nearly 95% showed opposite transcription patterns with physical activity compared to Aging/AD. The majority (>70%) of these anti-Aging/AD genes showed increased expression with physical activity and decreased expression in Aging/AD. Enrichment analysis of the anti-Aging/AD genes showing increased expression in association with physical activity revealed strong overrepresentation of mitochondrial energy production and synaptic function, along with axonal function and myelin integrity. Synaptic genes were notably enriched for synaptic vesicle priming, release and recycling, glutamate and GABA signaling and synaptic spine plasticity. Anti-Aging/AD genes showing decreased expression in association with physical activity were enriched for transcription-related function. These data suggest that physical activity preserves a more youthful profile in the hippocampus across multiple biological processes, providing a potential molecular foundation for how physical activity can delay age- and AD-related decline of hippocampal function.
2018-12-31 | GSE110298 | GEO
Project description:Understanding the pathological basis of the neurological symptoms observed following SARS-CoV2 infection is essential to optimizing outcomes and developing therapeutics. We performed proteomics profiling across eight cortical and subcortical brain regions, frontal lobe, temporal lobe, occipital lobe, hippocampus, thalamus, basal ganglia, midbrain, and pons, using postmortem brain samples from severe acute COVID-19 patients and matched controls (n=16), all preserved as formalin-fixed paraffin-embedded (FFPE) tissue. Integrating proteomics and additional transcriptomic analyses, we identified board dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and changes exhibited similarities with those seen in various age-related neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD).
2024-03-12 | MSV000094297 | MassIVE
Project description:Alzheimer’s disease (AD) is a severe1 age-related neurodegenerative disorder characterized by accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles, synaptic and neuronal loss, and cognitive decline. Several genes have been implicated in AD, but chromatin state alterations during neurodegeneration remain uncharacterized. Here, we profile transcriptional and chromatin state dynamics across early and late pathology in the hippocampus of an inducible mouse model of AD-like neurodegeneration. We find a coordinated downregulation of synaptic plasticity genes and regulatory regions, and upregulation of immune response genes and regulatory regions, which are targeted by factors that belong to the ETS family of transcriptional regulators, including PU.1. Human regions orthologous to increasing-level enhancers show immune cell-specific enhancer signatures as well as immune cell expression quantitative trait loci (eQTL), while decreasing-level enhancer orthologs show fetal brain specific enhancer activity. Surprisingly, AD-associated genetic variants are specifically enriched in increasing-level enhancer orthologs implicating immune processes in AD predisposition. Indeed, increasing enhancers overlap known AD loci lacking protein-altering variants and implicate additional loci that do not reach genome-wide significance. Our results reveal new insights into the mechanisms of neurodegeneration and establish the mouse as a useful model for functional studies of AD regulatory regions. We profiled gene expression levels through RNA-Seq and histone mark levels through ChIP-Seq to compare control mice to the CK-p25 Alzheimer's disease model at 2 weeks and 6 weeks after induction of neurodegeneration.
2015-02-18 | E-GEOD-65159 | biostudies-arrayexpress
Project description:We measured RNA synaptic localization differences in human AD patient samples. We performed RNA sequencing to identify mislocalized coding and non-coding RNAs and contrasted findings with global expression differences in human frontal and temporal lobe tissue as well as an APP/PSEN1 AD mouse model. We discovered significant mRNA localization differences in AD tissue including upregulation of genes related to cell differentiation and adhesion, and downregulation of genes related to cellular component organization ion transport. In addition, we identified major differences among circular RNAs (circRNAs) localized to synapses. Among our data, we discovered two unique isoforms of circGSK3β that are differentially expressed in AD. Furthermore, we found that expression of these distinct isoforms affects tau phosphorylation in neural cell culture. These discoveries substantiate the importance of circRNAs in the brain and in neurodegenerative disease. Identifying differences in synaptic-localized mRNAs and circRNAs opens new avenues to understanding AD synaptic pathology and identifying potential therapeutic targets.
2023-07-18 | GSE237258 | GEO
Project description:Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is pathologically characterized by amyloid β-peptide (Aβ)-containing plaques and the generation of neurofibrillary tangles (NFTs). Although proteome profile changes have been reported in AD brains, it is unclear whether they represent a continuous process from mild to severe changes or whether there is a sequence, with step-by-step involvement of proteins. To address this we analyzed neocortex samples of 19 control cases without signs of neurodegeneration (nonAD), 17 pathologically-diagnosed preclinical AD (p-preAD), and 17 symptomatic AD cases by mass spectrometry after homogenization and separation into soluble, dispersible, membrane-associated, and plaque-associated fractions. Here, we show three classes of proteins exhibiting changed levels during the pathogenesis and progression of AD from the AD pathology-free to the symptomatic stage: five early- and 24 late-responding proteins and 17 gradually changing proteins. The identified proteins and hierarchy point to endocytosis/synaptic vesicle cycle-related processes as key elements in the initiation of AD pathology in the neocortex, while later changes document the resulting neurodegenerative process.
2021-06-21 | PXD020020 | Pride
Project description:Age-related decline occurs in most brain structures and sensory systems. An illustrative case is olfaction, where the olfactory bulb (OB) undergoes deterioration with age, resulting in reduced olfactory ability. A decline in olfaction is also associated with early symptoms of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the underlying reasons are unclear. The microphthalmia-associated transcription factor (MITF) is expressed in the projection neurons (PNs) of the OB – the mitral and tufted (M/T) cells. Primary M/T cells from Mitf mutant mice show hyperactivity, potentially attributed to reduced expression of a key potassium channel subunit, Kcnd3/Kv4.3. This influences intrinsic plasticity, an essential mechanism involving the non-synaptic regulation of neuronal activity. As neuronal hyperactivity often precedes neurodegenerative conditions, the current study aimed to determine whether the absence of Mitf has degenerative effects during aging. Aged Mitf mutant mice showed reduced olfactory ability without inflammation. However, an increase in the expression of potassium channel subunit genes in the OBs of aged Mitfmi-vga9/mi-vga9 mice suggests that during aging compensatory mechanisms lead to stabilization.
2024-09-25 | GSE277734 | GEO
Project description:In neurodegenerative disorders such as Alzheimer’s disease (AD), brain miRNA profiles are altered; thus miRNA dysfunction could be both a cause and a consequence of disease. Our study dissects the complexity of human AD pathology, in the absence of a post mortem delay, and provides the first miRNA profiling analysis addressing the contribution of amyloid-β (Aβ), a known causative factor of AD, to the de-regulation of neuronal miRNA expression. We used murine primary hippocampal neurons to show that Aβ is a powerful regulator of mature miRNA expression and a prominent miRNA down-regulation is evoked in response to Aβ peptides. Our study provides insight into a previously unexplored mechanism of how Aβ may impact the pathology of AD and identification of key miRNAs affected by Aβ will allow further analysis on target genes and biological pathways contributing to AD pathomechanisms.
2010-05-30 | GSE20447 | GEO
Project description:The master epigenetic regulator lysine acetyltransferase (KAT) p300/CBP plays a pivotal role in neuroplasticity and cognitive functions. Recent evidence has shown that in several neurodegenerative diseases, including Alzheimer’s disease (AD), the expression level and function of p300/CBP are severely compromised, leading to altered gene expression causing pathological conditions. Here, we show that p300/CBP activation by a small molecule TTK21, conjugated to carbon nanosphere (CSP) ameliorates Aβ-impaired long-term potentiation (LTP) induced by high frequency stimulation, theta burst stimulation and synaptic tagging/capture (STC). This functional rescue was correlated with CSP-TTK21induced changes in transcription and translation. Mechanistically, we observed that the expression of a large number of synaptic plasticity- and memory-related genes was rescued, presumably by the restoration of p300/CBP mediated acetylation. Collectively, these results suggest that small molecule activators of p300/CBP could be a potential therapeutic molecule for neurodegenerative diseases like AD
2024-06-02 | GSE206799 | GEO
Project description:Microglia are innate immune cells of the brain that perform phagocytic and inflammatory functions in disease conditions. Transcriptomic studies of acutely-isolated microglia have provided novel insights into their molecular and functional diversity in homeostatic and neurodegenerative disease states. State-of-the-art mass spectrometric methods can comprehensively characterize proteomic alterations in microglia in neurodegenerative disorders, potentially providing novel functionally-relevant molecular insights that are not provided by transcriptomics. However, proteomic profiling of adult primary microglia in neurodegenerative disease conditions has not been performed. We performed quantitative proteomic analyses of purified CD11b+ acutely-isolated microglia adult mice in normal, acute neuroinflammatory (LPS-treatment) and chronic neurodegenerative states (5xFAD model of Alzheimer’s disease [AD]) using tandem mass tag mass spectrometry. Differential expression analyses were performed to characterize specific microglial proteomic changes in 5xFAD mice and identify overlap with LPS-induced pro-inflammatory changes. Our results were also contrasted with existing proteomic data from wild-type mouse microglia and from existing microglial transcriptomic data from wild-type and 5xFAD mice. Neuropathological validation studies of select proteins were performed in human AD and 5xFAD brains. Of 4,133 proteins identified, 187 microglial proteins were differentially expressed in the 5xFAD mouse model of AD pathology, including proteins with previously known (Apoe, Clu and Htra1) as well as previously unreported relevance to AD biology (Cotl1 and Hexb). Proteins upregulated in 5xFAD microglia shared significant overlap with pro-inflammatory changes observed in LPS-treated mice. Several proteins increased in human AD brain were also upregulated by 5xFAD microglia (Aβ peptide, Apoe, Htra1, Cotl1 and Clu). Cotl1 was identified as a novel microglia-specific marker with increased expression and strong association with AD neuropathology. Apoe protein was also detected within plaque-associated microglia in which Apoe and Aβ were highly co-localized suggesting a role for Apoe in phagocytic clearance of Aβ. We report the first comprehensive comparative proteomic study of adult mouse microglia derived from acute neuroinflammatory and AD models, representing a valuable resource to the neuroscience research community. We highlight shared and unique microglial proteomic changes in acute neuroinflammatory, aging and AD mouse models in addition to identifying novel roles for microglial proteins in human neurodegeneration.
2018-09-18 | PXD009137 | Pride
Project description:With the aging population, there is a growing focus on dementia, especially Alzheimer’s disease (AD). The molecular basis underlying the pathogenesis of AD is gradually being elucidated. Increasing evidence has shown that the immunological function of leukocytes plays a crucial role in the development of neurodegenerative disorders. However, there have been few studies among the Taiwanese population. The aim of this study was to investigate potential biomarkers for early diagnosis of Alzheimer’s disease from blood leukocytes. Experiment Overall Design: The peripheral blood mononuclear cells (PBMC) transcriptomes from 5 patients with mild cognitive impairment (MCI), 4 AD, as well as 4 normal controls (NC), were analyzed by microarray analysis.
2009-12-04 | E-GEOD-18309 | biostudies-arrayexpress