Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pin1 mediates Ab42-mediated dendritic spine loss

ABSTRACT: Early-stage Alzheimer's disease is characterized by the loss of dendritic spines in the neocortex of the brain. This phenomenon precedes tau pathology, plaque formation, and neurodegeneration and likely contributes to synaptic loss, memory impairment, and behavioral changes in patients. Studies suggest that spine loss is induced by soluble, multimeric Ab42, whose post-synaptic signaling activates the protein phosphatase calcineurin. We investigated how calcineurin causes spine pathology and found that the cis-trans prolyl isomerase Pin1 is a critical downstream target of Ab42/calcineurin signaling. In spines, Pin1 interacts with and is dephosphorylated by calcineurin, which rapidly suppresses its isomerase activity. Pin1 knockout or Ab42 exposure induced mature spine loss in Ab42-treated wild-type cells but had no effect on Pin1 null neurons. The data implicate Pin1 in spine maintenance and synaptic loss in early Alzheimer's disease.

INSTRUMENT(S): orbitrap fusion lumos

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: James S. Malter

PROVIDER: MSV000082066 | MassIVE | Wed Feb 14 11:11:00 GMT 2018

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

S-SCAM is essential for synapse formation

Project description:Synapse formation is critical for the wiring of neural circuits in the developing brain. The synaptic scaffolding protein S-SCAM/MAGI-2 has important roles in the assembly of signaling complexes at postsynaptic densities. However, the role of S-SCAM in establishing the entire synapse is not known. Here, we report significant effects of RNAi-induced S-SCAM knockdown on the number of synapses in early stages of network development in vitro. In vivo knockdown during the first three postnatal weeks reduced the number of dendritic spines in the rat brain neocortex. Knockdown of S-SCAM in cultured hippocampal neurons severely reduced the clustering of both pre- and postsynaptic components. This included synaptic vesicle proteins, pre- and postsynaptic scaffolding proteins, and cell adhesion molecules, suggesting that entire synapses fail to form. Correspondingly, functional and morphological characteristics of developing neurons were affected by reducing S-SCAM protein levels: neurons displayed severely impaired synaptic transmission and reduced dendritic arborization. A next generation sequencing approach showed normal expression of housekeeping genes, but changes of expression levels in 39 synaptic signaling molecules in cultured neurons. These results indicate that S-SCAM mediates the recruitment of all key classes of synaptic molecules during synapse assembly and is critical for the development of neural circuits in the developing brain.

2023-10-02 | GSE228093 | GEO

Enhancing WNT-Signaling Restores Cortical Neuronal Spine Maturation and Synaptogenesis in Tbr1 Mutants

Project description:Tbr1 is a high confidence autism spectrum disorder (ASD) gene encoding a transcription factor with distinct pre- and postnatal functions. Postnatally, Tbr1 conditional mutants (CKOs) and constitutive heterozygotes have immature dendritic spines and reduced synaptic density. Tbr1 regulates expression of several genes that underlie synaptic defects, including a kinesin (Kif1a) and a WNT signaling ligand (Wnt7b). Furthermore, Tbr1 mutant corticothalamic neurons have reduced thalamic axonal arborization. LiCl and a GSK3b-inhibitor, two WNT-signaling agonists, robustly rescue the dendritic spines, synaptic and axonal defects, suggesting that this could have relevance for therapeutic approaches in some forms of ASD.

2020-03-04 | GSE146298 | GEO

Alzheimer disease neocortex LC-MSMS

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

Temporal lobe epilepsy and Alzheimer's disease

Project description:This SuperSeries is composed of the following subset Series: GSE6771: Temporal Cortex Control (mesial temporal lobe epilepsy control) GSE6773: Temporal neocortex mesial temporal lobe epilepsy GSE6774: Temporal Cortex Control (Alzheimer's disease control) GSE6775: Temporal Cortex Alzheimer's Disease GSE6777: Cerebellum Alzheimer's Disease GSE6778: Cerebellum Control (Alzheimer's disease control) Keywords: SuperSeries Refer to individual Series

2007-01-23 | E-GEOD-6834 | biostudies-arrayexpress

Activity-induced Nr4a1 regulates spine density and distribution pattern of excitatory synapses in pyramidal neurons

Project description:Excitatory synapses occur mainly on dendritic spines, and spine density is usually correlated with the strength of excitatory synaptic transmission. We report that Nr4a1, an activity-inducible gene encoding a nuclear receptor, regulates the density and distribution of dendritic spines in CA1 pyramidal neurons. Nr4a1 overexpression resulted in elimination of the majority of spines; however, postsynaptic densities were preserved on dendritic shafts, and the strength of excitatory synaptic transmission was unaffected, showing that excitatory synapses can be dissociated from spines. mRNA expression profiling studies suggest that Nr4a1-mediated transcriptional regulation of the actin cytoskeleton contributes to this effect. Under conditions of chronically elevated activity, when Nr4a1 was induced, Nr4a1 knockdown increased the density of spines and PSDs specifically at the distal ends of dendrites. Thus, Nr4a1 is a key component of an activity-induced transcriptional program that regulates the density and distribution of spines and synapses. After 10 days in culture, dissociated mouse hippocampal neurons in 6-well plates were infected with lentivirus expressing either Flag-Nr4a1 or GFP and incubated for 6 days to allow for transgene expression. Total RNA was then isolated using RNeasy Plus kit (QIAGEN). Samples passing an mRNA quality check proceeded to quantitative analysis on Agilent-026655 4x44 Mouse Microarrays.

2016-01-13 | E-GEOD-76805 | biostudies-arrayexpress

RNA-seq raw data and analysis for APP, Shal495 and TrpA1 Drosophila melanogaster mutants

Project description:Evidence suggests that impaired synaptic and firing homeostasis represents a driving force of early Alzheimer’s disease (AD) progression. Here, we examine synaptic and sleep homeostasis in a Drosophila model by overexpressing human amyloid precursor protein (APP), whose duplication and mutations cause familial early-onset AD. We find that APP overexpression induces synaptic hyperexcitability. RNA-seq data indicate exaggerated expression of Ca2+ related signaling genes in APP mutants, including genes encoding Dmca1D, calcineurin (CaN) complex, and IP3R, but not in hyperexcitable mutants caused by TrpA1 or Shal/Kv4. We further demonstrate that increased CaN activity triggers transcriptional activation of Itpr (IP3R) through activating nuclear factor of activated T cells (NFAT). Strikingly, APP overexpression causes defects in both synaptic downscaling and sleep deprivation induced sleep rebound, and both defects could be restored by inhibiting IP3R. Our findings uncover IP3R as a shared signaling molecular in synaptic downscaling and sleep homeostasis, and its dysregulation may lead to synaptic hyperexcitability and AD progression at early stage.

2022-02-18 | GSE196770 | GEO

Activity-induced Nr4a1 regulates spine density and distribution pattern of excitatory synapses in pyramidal neurons

2016-01-13 | GSE76805 | GEO

study of actin interactome in Alzheimers disease mouse model

Project description:Filamentous actin (F-actin) is one of the major cytoskeleton proteins present in dendritic spines and it is an essential component for defining dendritic spine morphology. We have shown that synaptosomal F-actin levels were significantly decreased in APP/PS1 mice as early as one month of age. The molecular mechanisms involved in F-actin loss in synaptosomes, the underlying factors and the functional consequence involved needs to be elucidated. Synaptic neurotransmission and synaptic plasticity are dependent on the dynamic regulation of the actin through actin interacting and actin-modulating proteins. F-actin nanoarchitecture is regulated by several factors, such as reactive oxygen species and cofilin and others that are present in the dendritic spines. Yet, the key players and their role in synaptosomal F-actin organization remains unknown. Here, we characterized actin interactome from wild type and APP/PS1 male mice.

2024-10-17 | PXD050802 | Pride

Mus musculus

Project description:STING-Signaling Participates in Early Microglial Activation and Lysosome Dysfunction in Alzheimer's Amyloid Pathology

| PRJNA634986 | ENA

Long noncoding RNA microarray profile in the plasma of mild cognitive impairment due to Alzheimer's disease

Project description:To explore the lncRNAs associated with pathology of early Alzheimer's disease, we detected the lncRNA profiles in the plasma of subjects with mild cognitive impairment due to Alzheimer's disease and gender-, age-, education-matched normal control elderly.

2023-03-01 | GSE225304 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data