PXD032832-1

PXD032832 is an original dataset announced via ProteomeXchange.

Title	Glycation modulates glutamatergic signaling and exacerbates Parkinson’s disease-like phenotypes
Description	Alpha-synuclein (aSyn) is a central player in the pathogenesis of synucleinopathies due to its accumulation in typical protein aggregates in the brain. However, it is still unclear how it contributes to neurodegeneration. Type-2 diabetes mellitus is a risk factor for Parkinson’s disease (PD) and, interestingly, a common molecular alteration among these disorders is the age-associated increase in protein glycation. We hypothesized that glycation-induced neuronal dysfunction might be a contributing factor in synucleinopathies. Here, we dissected the specific impact of methylglyoxal (MGO, a glycating agent) in mice overexpressing aSyn in the brain. We found that MGO-glycation potentiates motor, cognitive, olfactory, and colonic dysfunction in aSyn transgenic (Thy1-aSyn) mice that received a single dose of MGO via intracerebroventricular (ICV) injection. aSyn accumulates in the midbrain, striatum, and prefrontal cortex, and protein glycation is increased in the cerebellum and midbrain. SWATH mass spectrometry analysis, used to quantify changes in the brain proteome, revealed that MGO mainly increase glutamatergic-associated proteins in the midbrain (NMDA, AMPA, glutaminase, VGLUT and EAAT1), but not in the prefrontal cortex, where it mainly affects the electron transport chain. Notably, the glycated proteins in the midbrain of Thy1-aSyn mice that received MGO strongly correlate with PD and dopaminergic pathways. Overall, we demonstrated that MGO-induced glycation accelerates PD-like sensorimotor and cognitive alterations and suggest that the increase of glutamatergic signaling may underly these events. Our study sheds new light into the enhanced vulnerability of the midbrain in PD-related synaptic dysfunction and suggests that glycation suppressors and anti-glutamatergic drugs may hold promise as disease-modifying therapies for synucleinopathies.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-20_13:16:35.981.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hugo Vicente Miranda
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-26 14:33:17	ID requested
⏵ 1	2022-05-20 13:16:38	announced

Cheg, ã, o A, Guarda M, Alexandre BM, Shvachiy L, Temido-Ferreira M, Marques-Morgado I, Fernandes Gomes B, Matthiesen R, Lopes LV, Florindo PR, Gomes RA, Gomes-Alves P, Coelho JE, Outeiro TF, Vicente Miranda H, Glycation modulates glutamatergic signaling and exacerbates Parkinson's disease-like phenotypes. NPJ Parkinsons Dis, 8(1):51(2022) [pubmed]

submitter keyword: Glycation, Parkinson's disease, Brain

Hugo Vicente Miranda
contact affiliation	Dysmetabolism in Brain Diseases Lab, CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Rua Câmara Pestana, Nº 6, Edifício CEDOC II, Office 2.27, 1150-082 Lisboa, Portugal
contact email	hmvmiranda@nms.unl.pt
lab head
Hugo Vicente Miranda
contact affiliation	NOVA Medical School, Universidade NOVA de Lisboa
contact email	hmvmiranda@nms.unl.pt
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/2022/05/PXD032832

PRIDE project URI

• PRIDE
  1. PXD032832
     1. Label: PRIDE project
     2. Name: Glycation modulates glutamatergic signaling and exacerbates Parkinson’s disease-like phenotypes