PXD022221-1

PXD022221 is an original dataset announced via ProteomeXchange.

Title	Regulating hippocampal levels of Alzheimer´s disease-related proteins with a brain-penetrating somatostatin peptide
Description	Plaques consisting of amyloid-β (Aβ) in the brain are characteristic for patients with Alzheimer´s disease. Aβ is enzymatically generated of the amyloid precursor protein. Furthermore, neprilysin, an Aβ-degrading enzyme, and its main activator the neuropeptide somatostatin (SST) are downregulated in Alzheimer´s disease. In the fusion protein SST-scFv8D3, SST is recombinantly fused to a blood-brain barrier transporter. The aim of this study was to study the effect of SST-scFv8D3 on the proteome of different brain regions in order to elucidate the anti-Alzheimer´s disease effects of this construct. SST-scFv8D3 and phosphate buffered saline (PBS) respectively were injected into transgenic mice of an Alzheimer´s disease model with the Swedish mutation (AβPP KM670/671NL) every 36 hours (three times in total). Homogenates of the hippocampus, the cerebellum and the rest of the cerebrum were lysed. Afterwards, filter aided tryptic digestion was performed. The resulting peptides were analyzed using LC-UDMSE. The data was searched against a randomized mouse database and label-free quantification analysis was done. In total 1869 proteins were found. Only the proteome of the hippocampus was affected by the treatment with SST-scFv8D3. 55 proteins were significantly up and 105 down regulated compared to the PBS treated mice. Among these were mitochondrial and synaptic proteins as well as some involved in neuron´s development indicating anti-Alzheimer disease effects of SST-scFv8D3 and supporting the future use of SST-scFv8D3 as a treatment option.
HostingRepository	PRIDE
AnnounceDate	2021-06-28
AnnouncementXML	Submission_2021-06-28_02:57:15.230.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022221
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Erik Jansson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	carboxylated residue; amidated residue; monohydroxylated residue; acetylated residue; deamidated residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-28 03:50:21	ID requested
⏵ 1	2021-06-28 02:57:15	announced
2	2021-06-28 06:42:49	announced	2021-06-28: Updated project metadata.

10.1021/ACSCHEMNEURO.1C00303;

submitter keyword: Alzheimer´s disease, brain, mice, LC-MS, tryptic digestion, amyloid-β, neprilysin, SST-scFv8D3

Erik T. Jansson
contact affiliation	Department of Pharmaceutical Biosciences Uppsala University
contact email	erik.jansson@farmbio.uu.se
lab head
Erik Jansson
contact affiliation	Uppsala University
contact email	erik.jansson@farmbio.uu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022221
     1. Label: PRIDE project
     2. Name: Regulating hippocampal levels of Alzheimer´s disease-related proteins with a brain-penetrating somatostatin peptide