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PXD043963

PXD043963 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNative-state proteomics of Parvalbumin interneurons identifies novel molecular signatures and metabolic vulnerabilities to early Alzheimer's disease pathology
DescriptionOne 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
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:32:04.978.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJuliet Santiago
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue; acetylated residue; deamidated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-20 12:35:15ID requested
12024-03-04 08:52:10announced
22024-10-22 06:32:05announced2024-10-22: Updated project metadata.
Publication List
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]
Keyword List
submitter keyword: Alzheimer’s disease,Parvalbumin interneurons, proteomics
Contact List
Srikant Rangaraju
contact affiliationAssociate Professor, Department of Neurology, Emory University
contact emailsrikant.rangaraju@emory.edu
lab head
Juliet Santiago
contact affiliationEmory University
contact emailjvsanti@emory.edu
dataset submitter
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Dataset FTP location
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