PXD010415-3

PXD010415 is an original dataset announced via ProteomeXchange.

Title	Comprehensive Molecular Analysis of Tissue from Epileptic Patients Indicates Disruption of Energy, Redox and Purine Metabolism in Seizure Onset Comprehensive Molecular Analysis of Tissue from Epileptic Patients Indicates Disruption of Energy, Redox and Purine Metabolism in Seizure Onset
Description	Epilepsy is a disorder that affects around 1% of the population. Epilepsy is widely controlled by anti-convulsant drugs; however, approximately one third of patients do not respond to this treatment. In many cases of drug resistant epilepsy (DRE) surgical removal of the indicated tissue may be performed to decrease seizure burden. Mitochondrial damage and oxidative stress has been implicated in epilepsy suggesting that alternation in both energy metabolism and redox balance are critical to seizure onset. To understand the underlying biological processes involved in DRE, a combination of proteomics and metabolomics strategies together with oxidative damage assessment were used to compare molecular differences and enzymatic activities in tissue implicated in seizure onset to tissue with no abnormal activity within patients. Label free quantitation identified 17 proteins with altered abundance in the seizure onset zone as compared to tissue with normal activity. Assessment of oxidative protein damage by protein carbonylation identified additional 11 proteins with potentially altered function in the seizure onset zone. Pathway analysis revealed that most of the affected proteins are involved in energy metabolism and redox balance. Further enzymatic assays showed significantly decreased activity of transketolase (TKT) indicating a disruption of the Pentose Phosphate Pathway and diversion of intermediates into purine metabolic pathway, resulting in the generation of the potentially pro-convulsant metabolites. Altogether, these findings suggest that imbalance in energy metabolism and redox balance, pathways critical to proper neuronal function, play important roles in neuronal network hyperexcitability and can be used as a primary target for potential therapeutic strategies to combat DRE.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:35:14.987.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ryan Grove
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ; Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-13 02:21:22	ID requested
1	2022-03-07 02:07:05	announced
2	2023-11-14 08:49:56	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:35:15	announced	2024-10-22: Updated project metadata.

10.1016/J.JPROT.2020.103812;

curator keyword: Biomedical

submitter keyword: Human

brain

LC-MS/MS

MSe

Jiri Adamec
contact affiliation	University of Nebraska, Lincoln
contact email	jadamec2@unl.edu
lab head
Ryan Grove
contact affiliation	UNL
contact email	rgrove2@unl.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010415
     1. Label: PRIDE project
     2. Name: Comprehensive Molecular Analysis of Tissue from Epileptic Patients Indicates Disruption of Energy, Redox and Purine Metabolism in Seizure Onset Comprehensive Molecular Analysis of Tissue from Epileptic Patients Indicates Disruption of Energy, Redox and Purine Metabolism in Seizure Onset