PXD068754-1

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

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PRIDE project URI

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