PXD027583-1

PXD027583 is an original dataset announced via ProteomeXchange.

Title	Comparative proteomics of APBD and heathy control cells treated or not with 144DG11 under different conditions
Description	This project employs Adult Polyglucosan Body Disease (APBD) models to explore the efficacy and mechanism of action of the polyglucosan-reducing compound 144DG11. APBD is a glycogen storage disorder (GSD) caused by glycogen branching enzyme (GBE) deficiency causing accumulation of poorly branched glycogen inclusions called polyglucosans. 144DG11 improved survival and motor parameters in a GBE knockin (Gbeys/ys) APBD mouse model. 144DG11 reduced polyglucosan and glycogen in brain, liver, heart, and peripheral nerve. Indirect calorimetry experiments revealed that 144DG11 increases carbohydrate burn at the expense of fat burn, suggesting metabolic mobilization of pathogenic polyglucosan. At the cellular level, 144DG11 increased glycolytic, mitochondrial, and total ATP production. The molecular target of 144DG11 is the lysosomal membrane protein LAMP1, whose interaction with the compound, similar to LAMP1 knockdown, enhanced autolysosomal degradation of glycogen and lysosomal acidification. 144DG11 also enhanced mitochondrial activity and modulated lysosomal features as revealed by bioenergetic, image-based phenotyping and proteomics analyses. The results submitted to Pride are the raw LC-MS proteomics data of skin fibroblasts derived from APBD and healthy control subjects treated or not with 144DG11 under starvation or glycogen burden (starvation followed by glucose supplementation) conditions.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_05:47:49.194.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Or Kakhlon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-27 07:08:09	ID requested
⏵ 1	2022-02-17 05:47:50	announced

Kakhlon O, Vaknin H, Mishra K, D'Souza J, Marisat M, Sprecher U, Wald-Altman S, Dukhovny A, Raviv Y, Da'adoosh B, Engel H, Benhamron S, Nitzan K, Sweetat S, Permyakova A, Mordechai A, Akman HO, Rosenmann H, Lossos A, Tam J, Minassian BA, Weil M, Alleviation of a polyglucosan storage disorder by enhancement of autophagic glycogen catabolism. EMBO Mol Med, 13(10):e14554(2021) [pubmed]

submitter keyword: human skin fibroblasts, LC-MS, APBD, 144DG11

Or Kakhlon
contact affiliation	Dept. of Neurology Hadassah-Hebrew University Medical Center Ein Kerem Jerusalem 91120 Israel
contact email	ork@hadassah.org.il
lab head
Or Kakhlon
contact affiliation	Hadassah-Hebrew University Medical Center
contact email	ork@hadassah.org.il
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/2022/02/PXD027583

PRIDE project URI

• PRIDE
  1. PXD027583
     1. Label: PRIDE project
     2. Name: Comparative proteomics of APBD and heathy control cells treated or not with 144DG11 under different conditions