Dataset Information

Proteomic analysis of the entorhinal cortex and CA1 subfields of the hippocampus of macaques injected with tau seeds from Alzheimer’s brain

ABSTRACT: The "prion-like" features of Alzheimer’s disease (AD) tauopathy and its relationship with amyloid β (Aβ) has never been experimentally studied in primates phylogenetically close to humans. We injected 17 macaques in the entorhinal cortex with nanograms of tau proteopathic seeds purified from AD brains or control extracts from aged-matched healthy brains, with or without intracerebroventricular co-injections of recombinant Aβ oligomers. After neuropathological examination of the macaque’s brain, we also performed mass spectrometry-based proteomics of macaques’ entorhinal cortex and CA1 to study the spatial response (local and distant) to tau seeds injections (and its modulation by oligomeric Aβ).

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Macaca Mulatta (rhesus Macaque)

TISSUE(S): Brain

SUBMITTER: Stephane Claverol

LAB HEAD: Claverol Stephane

PROVIDER: PXD040522 | Pride | 2024-01-02

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 69

Similar Datasets

Project description:Cellular functional pathways have evolved through selection based on fitness benefits conferred through protein intra- and inter-molecular interactions that comprise all protein conformational features and protein-protein interactions, collectively referred to as the interactome. While the interactome is regulated by proteome levels, it is also regulated independently by, post translational modification, co-factor, and ligand levels, as well as local protein environmental factors, such as osmolyte concentration, pH, ionic strength, temperature and others. In modern biomedical research, cultivatable cell lines have become an indispensable tool, with selection of optimal cell lines that exhibit specific functional profiles being critical for success in many cases. While it is clear that cell lines derived from different cell types have differential proteome levels, increased understanding of large-scale functional differences requires additional information beyond abundance level measurements, including how protein conformations and interactions are altered in certain cell types to shape functional landscapes. Here, we employed quantitative in vivo protein cross-linking coupled to mass spectrometry to probe large-scale protein conformational and interaction changes among three commonly employed human cell lines, HEK293, MCF-7, and HeLa cells. Isobaric quantitative Protein Interaction Reporter (iqPIR) technologies were used to obtain quantitative values of cross-linked peptides across three cell lines. These data illustrated highly reproducible (R2 values larger than 0.8 for all biological replicates) quantitative interactome levels across multiple biological replicates. We also measured protein abundance levels in these cells using data independent acquisition quantitative proteomics methods. Combining quantitative interactome and proteomics information allowed visualization of cell type-specific interactome changes mediated by proteome level adaptations as well as independently regulated interactome changes to gain deeper insight into possible drivers of these changes. Among the biggest detected alterations in protein interactions and conformations are changes in cytoskeletal proteins, RNA-binding proteins, chromatin remodeling complexes, mitochondrial proteins, and others. Overall, these data demonstrate the utility and reproducibility of quantitative cross-linking to study systems-level interactome variations. Moreover, these results illustrate how combined quantitative interactomics and proteomics can provide unique insight on cellular functional landscapes.

			Action	DRS
	vp220106_01b.raw	Raw
	vp220106_02b.raw	Raw
	vp220106_03b.raw	Raw
	vp220106_04b.raw	Raw
	vp220106_05.raw	Raw

Dataset Information

Proteomic analysis of the entorhinal cortex and CA1 subfields of the hippocampus of macaques injected with tau seeds from Alzheimer’s brain

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets