Dataset Information

SAPPa, a neuroprotective protein in the brain has widespread effects on the transcriptome and proteome of human iPSC-derived glutamatergic neurons related to memory mechanisms.

ABSTRACT: Secreted amyloid precursor protein alpha (sAPPa) processed from a parent human brain protein, APP, can modulate learning and memory. It has potential for development of a therapy preventing, delaying, or even reversing Alzheimer’s disease. In this study a comprehensive analysis to understand how it affects the transcriptome and proteome of the human neuron was undertaken. Human iPSC-derived glutamatergic neurons in culture were exposed to 1 nM sAPPa over a time course and changes in the transcriptome and proteome were identified with RNA sequencing and SWATH-MS respectively. A large subset (~30%) of differentially expressed transcripts and proteins were functionally involved with the molecular biology of learning and memory, consistent with reported links of sAPPa to memory enhancement, as well as neurogenic, neurotrophic and neuroprotective phenotypes in previous studies. Differentially expressed proteins included those encoded in previously identified Alzheimer’s risk genes, APP processing related proteins, proteins involved in synaptogenesis, neurotransmitters, receptors, synaptic vesicle proteins, cytoskeletal proteins, proteins involved in protein and organelle trafficking, and proteins important for cell signalling, transcriptional splicing, and functions of the proteosome and lysosome. We have identified a complex set of genes affected by sAPPa, which may aid further investigation into the mechanism of how this neuroprotective protein affects memory formation and how it might be used as an Alzheimer’s disease therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE197725 | GEO | 2022/03/04

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project 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.

Dataset Information

SAPPa, a neuroprotective protein in the brain has widespread effects on the transcriptome and proteome of human iPSC-derived glutamatergic neurons related to memory mechanisms.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets