PXD053150

PXD053150 is an original dataset announced via ProteomeXchange.

Title	Proteomic changes upon huntingtin lowering in human cortical neurons
Description	Despite growing descriptions of wild-type Huntingtin's (wt-HTT) roles in both adult brain function and, more recently, development, several clinical trials are exploring HTT-lowering approaches that target both wt-HTT and the mutant isoforms (mut-HTT) responsible for Huntington's disease (HD). This non-selective targeting is based on the autosomal dominant inheritance of HD, supporting the idea that mutant HTT exerts its harmful effects through a toxic gain-of-function or a dominant-negative mechanism. However, the precise amount of wt-HTT needed for healthy neurons in adults and during development remains unclear. In this study, we address this question by examining how wt-HTT loss affects human neuronal network formation, synaptic maturation, and homeostasis in vitro. Our findings establish a role of wt-HTT in the maturation of dendritic arborization and the acquisition of network-wide synchronized activity by human cortical neuronal networks modeled in vitro. Interestingly, the network synchronization defects only became apparent when more than two-thirds of the wt-HTT protein was depleted. Our study underscores the critical need to precisely understand wt-HTT's role in neuronal health. It also emphasizes the potential risks of excessive wt-HTT loss associated with non-selective therapeutic approaches targeting both wt and mutant HTT isoforms in HD patients.
HostingRepository	PRIDE
AnnounceDate	2025-03-25
AnnouncementXML	Submission_2025-03-25_02:55:08.221.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD053150
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Virginie Redeker
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-16 14:41:28	ID requested
⏵ 1	2025-03-25 02:55:10	announced

Lou, ç, ã M, El Akrouti D, Lemesle A, Louessard M, Dufour N, Baroin C, de la Fouchardi, è, re A, Cotter L, Jean-Jacques H, Redeker V, Perrier AL, Corrigendum to "Huntingtin lowering impairs the maturation and synchronized synaptic activity of human cortical neuronal networks derived from induced pluripotent stem cells" [Neurobiology of Disease Volume 200 (2024, Oct 1st) - Article# YNBDI_106630]. Neurobiol Dis, 202():106703(2024) [pubmed]

10.6019/PXD053150;

10.1016/j.nbd.2024.106703;

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Neuronal network

HTT lowering

Huntington disease

Huntingtin

pluripotent stem cell

synapse

proteome

nanoLC-MSMS

label free quantification of proteins

Anselme Perrier
contact affiliation	MIRCen, UMR9199, CEA, CNRS, Université Paris-Saclay
contact email	anselme.perrier@cea.fr
lab head
Virginie Redeker
contact affiliation	CNRS
contact email	virginie.redeker@cnrs.fr
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/2025/03/PXD053150

PRIDE project URI

• PRIDE
  1. PXD053150
     1. Label: PRIDE project
     2. Name: Proteomic changes upon huntingtin lowering in human cortical neurons