PXD043963

PXD043963 is an original dataset announced via ProteomeXchange.

Title	Native-state proteomics of Parvalbumin interneurons identifies novel molecular signatures and metabolic vulnerabilities to early Alzheimer's disease pathology
Description	One of the earliest pathophysiological perturbations in Alzheimer’s Disease (AD) may arise from dysfunction of fast-spiking parvalbumin (PV) interneurons (PV-INs). Defining early protein-level (proteomic) alterations in PV-INs can provide key biological and translationally relevant insights. Here, we use cell-type-specific in vivo biotinylation of proteins (CIBOP) coupled with mass spectrometry to obtain native-state proteomes of PV interneurons. PV-INs exhibited proteomic signatures of high metabolic, mitochondrial, and translational activity, with over-representation of causally linked AD genetic risk factors. Analyses of bulk brain proteomes indicated strong correlations between PV-IN proteins with cognitive decline in humans, and with progressive neuropathology in humans and mouse models of Aβ pathology. Furthermore, PV-IN-specific proteomes revealed unique signatures of increased mitochondrial and metabolic proteins, but decreased synaptic and mTOR signaling proteins in response to early Aβ pathology. PV-specific changes were not apparent in whole-brain proteomes. These findings showcase the first nativestate PV-IN proteomes in mammalian brain, revealing a molecular basis for their unique vulnerabilities in AD
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:32:04.978.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Juliet Santiago
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-20 12:35:15	ID requested
1	2024-03-04 08:52:10	announced
⏵ 2	2024-10-22 06:32:05	announced	2024-10-22: Updated project metadata.

10.1101/2023.05.17.541038;

Kumar P, Goettemoeller AM, Espinosa-Garcia C, Tobin BR, Tfaily A, Nelson RS, Natu A, Dammer EB, Santiago JV, Malepati S, Cheng L, Xiao H, Duong D, Seyfried NT, Wood LB, Rowan MJ, Rangaraju S, Native-state proteomics of Parvalbumin interneurons identifies novel molecular signatures and metabolic vulnerabilities to early Alzheimer's disease pathology. bioRxiv, ():(2023) [pubmed]

submitter keyword: Alzheimer’s disease,Parvalbumin interneurons, proteomics

Srikant Rangaraju
contact affiliation	Associate Professor, Department of Neurology, Emory University
contact email	srikant.rangaraju@emory.edu
lab head
Juliet Santiago
contact affiliation	Emory University
contact email	jvsanti@emory.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/03/PXD043963

PRIDE project URI

• PRIDE
  1. PXD043963
     1. Label: PRIDE project
     2. Name: Native-state proteomics of Parvalbumin interneurons identifies novel molecular signatures and metabolic vulnerabilities to early Alzheimer's disease pathology