PXD005675

PXD005675 is an original dataset announced via ProteomeXchange.

Title	Elucidation of the inflammatory and neuroprotective molecular network of TNFalpha in neurons related to Alzheimer´s disease
Description	Neuroinflammation is a hallmark of various neurological diseases such as Alzheimer’s disease. The aim of the study was to elucidate the dose-dependent in vitro molecular mechanism of TNFα in neurons related to neuroprotection and -degeneration. We performed a quantitative proteomics and phospho-proteomics study in HT22 neuronal cells as well as differentiated human neurons to elucidate alterations in TNFα dose-dependent (0.1 – 100.0 ng/ml) signaling pathways. We report here that 10.0 ng/ml TNFα reduces mitochondrial signaling and inhibits protein translation signaling related to mTOR but leads also at the same time to induction of neuroprotective MAPK-CREB signaling after 24 hours in HT22 cells. Stimulation of TNFα (1.0 ng/ml, 24 hours) in human neurons reveals similar cellular mechanisms on protein translation signaling related to mTOR as seen in HT22 cells at 10.0 ng/ml dose whereas mitochondrial membrane potential and reactive oxygen species level were not changed. SiRNA-mediated knockdown of CREB in human neurons prior to TNFα stimulation led to a reduced number of protein/phospho-protein hits compared to siRNA-mediated knockdown of CREB or TNFα stimulation alone and countermeasures the reduced CREB signaling. In vivo data of TNFα knock-out transgenic mice showed that learning ability does not depend on TNFα during normal aging but that TNFα preserves the learning and memory ability during episodes of systemic inflammation resembling the persistent neuroinflammation status as seen in Alzheimer´s disease. This may be based on modulation of CREB as revealed by our in vitro studies. Our data indicate that several molecular targets and signaling pathways induced by TNFα in neurons resemble those of Alzheimer´s pathology. It may suggest that TNFα functions as a contributing factor to this neurodegenerative disease but has also at the same time neuroprotective properties regulating learning and memory formation under neuroinflammatory status.
HostingRepository	PRIDE
AnnounceDate	2017-08-08
AnnouncementXML	Submission_2017-08-08_13:24:10.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefan J. Kempf
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-01-09 06:29:21	ID requested
⏵ 1	2017-08-08 13:24:11	announced

curator keyword: Biomedical

submitter keyword: CREB, mTOR, neuroinflammation, TNFα, Alzheimer´s disease, phosphoproteomics

Martin R. Larsen
contact affiliation	Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
contact email	mrl@bmb.sdu.dk
lab head
Stefan J. Kempf
contact affiliation	University of Southern Denmark
contact email	stefank@bmb.sdu.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005675
     1. Label: PRIDE project
     2. Name: Elucidation of the inflammatory and neuroprotective molecular network of TNFalpha in neurons related to Alzheimer´s disease