PXD068754

PXD068754 is an original dataset announced via ProteomeXchange.

Title	The Nodding Syndrome Cerebrospinal Fluid Proteome: A Lens into Neurodevelopmental Failure
Description	Nodding Syndrome (NS), a pediatric epileptic encephalopathy of East Africa, has long defied etiological classification. Here, we report high-resolution untargeted proteomics of cerebrospinal fluid from Ugandan NS patients and controls that reveals widespread disruption across immune, proteostatic, synaptic, metabolic, transcriptional, and neurovascular domains, with tauopathy as a secondary amplifier. This molecular signature closely resembles MECP2 duplication syndrome (MDS), an X-linked disorder of methyl-CpG binding protein 2 (MECP2) overexpression characterized by systemic immune-metabolic dysfunction and tau instability. Importantly, NS also shares features with Rett syndrome, the genetic converse of MDS, which results from MECP2 loss-of-function mutations or underexpression. Together, these parallels position NS along a MECP2 dysregulation axis, wherein dosage imbalance destabilizes convergent neurodevelopmental and systemic pathways. We propose that NS represents an environmentally imprinted phenocopy of MECP2-axis collapse, primed by prenatal maternal immune activation (MIA) and exacerbated by postnatal malnutrition, biotoxin exposures, and nematode and other infections. This framework repositions NS as a multisystem disorder of environmentally-driven MECP2 dysregulation, bridging genetic and environmental paradigms of tauopathy, and opening new avenues for multipronged intervention.
HostingRepository	PRIDE
AnnounceDate	2026-01-20
AnnouncementXML	Submission_2026-01-20_13:13:22.608.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-23 20:20:28	ID requested
⏵ 1	2026-01-20 13:13:23	announced

Dataset with its publication pending

submitter keyword: epilepsy, MARS-14 depletion, SPS-MS3, Cerebrospinal fluid (CSF), mass spectrometry, MIA, biotoxins, tauopathy, neurodevelopment, TMTpro, Nodding syndrome, MECP2, isobaric labeling quantitative proteomics

Angues R Valdes
contact affiliation	Department of Neurology School of Medicine Oregon Health & Science University Portland, OR, USA
contact email	valdesr@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.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/2026/01/PXD068754

PRIDE project URI

• PRIDE
  1. PXD068754
     1. Label: PRIDE project
     2. Name: The Nodding Syndrome Cerebrospinal Fluid Proteome: A Lens into Neurodevelopmental Failure