PXD072104

PXD072104 is an original dataset announced via ProteomeXchange.

Title	mTOR inhibition ameliorates tau burden and neurofilament pathology in sporadic PSP-RS neurons
Description	Progressive supranuclear palsy, Richardson’s syndrome subtype (PSP-RS), is a tauopathy marked by early axonal pathology and neurodegeneration. Modeling sporadic PSP-RS in human neurons remained a major challenge. Here, we generated midbrain dopaminergic (mDA) neurons from induced pluripotent stem cells (iPSCs) derived from idiopathic PSP-RS patients and healthy controls. Combined transcriptomic and proteomic analysis revealed reduced dopaminergic differentiation and synaptic function, alongside increased phosphorylated and oligomeric Tau, neurofilament accumulation, axonal swelling, and endoplasmic reticulum disorganization. These alterations coincided with impaired autophagic flux and elevated levels of phosphorylated mTOR. Pharmacological inhibition of mTOR restored autophagy and reduced neurofilament and tau pathology. Collectively, our findings implicate mTOR-dependent autophagy dysfunction as a key driver of early axonal pathology of PSP-RS and highlight autophagy modulation as a promising therapeutic avenue.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-07_16:32:43.447.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Caterina Gabriele
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-17 09:40:59	ID requested
⏵ 1	2026-06-07 16:32:44	announced

Covello R, Benedetto GL, Scalise S, Gabriele C, Valente D, Zannino C, Puccio B, Quattrone A, Guzzi PH, Gaspari M, Quattrone A, Cuda G, Parrotta EI, Cytoskeletal Imbalance and Axonal Vulnerability in Sporadic PSP-RS: Early Changes in a Human iPSC-Derived Neuronal Model with Altered mTOR Signaling. Cells, 15(9):(2026) [pubmed]

10.3390/cells15090754;

submitter keyword: Tauopathy

Progressive supranuclear palsy

neurofilament

dopaminergic neurons

axonal degeneration

autophagy modulation

Marco Gaspari
contact affiliation	Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, 88100, Italy
contact email	gaspari@unicz.it
lab head
Caterina Gabriele
contact affiliation	Università Magna Graecia di Catanzaro
contact email	cgabriele86@gmail.com
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/2026/06/PXD072104

PRIDE project URI

• PRIDE
  1. PXD072104
     1. Label: PRIDE project
     2. Name: mTOR inhibition ameliorates tau burden and neurofilament pathology in sporadic PSP-RS neurons