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PXD072104-1

PXD072104 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlemTOR inhibition ameliorates tau burden and neurofilament pathology in sporadic PSP-RS neurons
DescriptionProgressive 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.
HostingRepositoryPRIDE
AnnounceDate2026-06-08
AnnouncementXMLSubmission_2026-06-07_16:32:43.447.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterCaterina Gabriele
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-12-17 09:40:59ID requested
12026-06-07 16:32:44announced
Publication List
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;
Keyword List
submitter keyword: Tauopathy
Progressive supranuclear palsy
neurofilament
dopaminergic neurons
axonal degeneration
autophagy modulation
Contact List
Marco Gaspari
contact affiliationDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, 88100, Italy
contact emailgaspari@unicz.it
lab head
Caterina Gabriele
contact affiliationUniversitĂ  Magna Graecia di Catanzaro
contact emailcgabriele86@gmail.com
dataset submitter
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Dataset FTP location
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