PXD016850

PXD016850 is an original dataset announced via ProteomeXchange.

Title	Temporal proteomic analyses of the protein contents found in the insoluble fraction of the a-synuclein PFF-treated neurons
Description	Parkinson’s disease (PD) is characterized by the accumulation of misfolded and aggregated alpha-synuclein (α-syn) into intraneuronal inclusions named Lewy bodies (LB). Although it is widely believed that α-syn plays a central role in the pathogenesis of PD, the processes that govern α-syn fibrillization and LB formation remain poorly understood. In this work, we sought to dissect the spatiotemporal events involved in the biogenesis of the LBs at the genetic, molecular, biochemical, structural, and cellular levels. Towards this goal, we further developed a seeding-based model of α-syn fibrillization to generate a neuronal model that reproduces all the key events leading to LB formation; including seeding, fibrillization, and the formation of inclusions that recapitulate many of the biochemical, structural, and organizational features of bona fide LBs. Using an integrative omics, biochemical and imaging approach, we dissected the molecular events associated with the different stages of LB formation and their contribution to neuronal dysfunction and degeneration. In addition, we demonstrate that LB formation involves a complex interplay between α-syn fibrillization, post-translational modifications, and interactions between α-syn aggregates and membranous organelles, including mitochondria, the autophagosome and endolysosome. Finally, we show that the process of LB formation, rather than simply fibril formation, is the major driver of neurodegeneration through disruption of cellular functions and inducing mitochondria damage and deficits, and synaptic dysfunctions. We believe that this model represents a powerful platform to further investigate the mechanisms of LB formation and clearance and to screen and evaluate novel therapeutics targeting α-syn aggregation and LB formation.
HostingRepository	PRIDE
AnnounceDate	2020-01-15
AnnouncementXML	Submission_2020-01-15_09:23:45.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hilal Lashuel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-19 06:56:35	ID requested
⏵ 1	2020-01-15 09:23:46	announced

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: Mouse Primary neurons

Hilal Lashuel
contact affiliation	LMNN, BMI, EPFL
contact email	hilal.lashuel@epfl.ch
lab head
Hilal Lashuel
contact affiliation	Ecole Polytechnique Fédérale de Lausanne
contact email	hilal.lashuel@epfl.ch
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/2020/01/PXD016850

PRIDE project URI

• PRIDE
  1. PXD016850
     1. Label: PRIDE project
     2. Name: Temporal proteomic analyses of the protein contents found in the insoluble fraction of the a-synuclein PFF-treated neurons