PXD031891-1

PXD031891 is an original dataset announced via ProteomeXchange.

Title	HIV-1 gp120 impairs spatial memory through CREB
Description	HIV-associated neurocognitive disorders (HAND) remain an unsolved problem that persists despite using antiretroviral therapy. We have obtained data showing that HIV-gp120 protein contributes to neurodegeneration through metabolic reprogramming. This led to decreased ATP levels, lower mitochondrial DNA copy numbers, and loss of mitochondria cristae, all-important for mitochondrial biogenesis. gp120 protein also disrupted mitochondrial movement and synaptic plasticity. Searching for the mechanisms involved, we found that gp120 alters the cyclic AMP response element-binding protein (CREB) phosphorylation on serine residue 133 necessary for its function as a transcription factor. Since CREB regulates the promoters of PGC1 and BDNF genes, we found that CREB dephosphorylation causes PGC1 and BDNF loss of functions. Our data was validated in vitro and in vivo. The negative effect of gp120 was alleviated in cells and animals in the presence of rolipram that inhibits the phosphodiesterase protein 4 (PDE4) and restores CREB phosphorylation. We concluded that HIV-gp120 protein contributes to HAND via inhibition of CREB protein function.
HostingRepository	PRIDE
AnnounceDate	2022-06-09
AnnouncementXML	Submission_2022-06-09_08:43:37.242.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD031891
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Carmen Merali
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-24 10:29:44	ID requested
⏵ 1	2022-06-09 08:43:38	announced

Shrestha J, Santerre M, Allen CNS, Arjona SP, Merali C, Mukerjee R, Chitrala KN, Park J, Bagashev A, Bui V, Eugenin EA, Merali S, Kaul M, Chin J, Sawaya BE, HIV-1 gp120 Impairs Spatial Memory Through Cyclic AMP Response Element-Binding Protein. Front Aging Neurosci, 14():811481(2022) [pubmed]

submitter keyword: Proteomics, HIV, neurodegeneration, CREB protein, Mitochondria, Rolipram

Salim Merali, Ph.D.
contact affiliation	Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Temple University
contact email	smerali@temple.edu
lab head
Carmen Merali
contact affiliation	Temple University
contact email	clmerali@temple.edu
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/2022/06/PXD031891

PRIDE project URI

• PRIDE
  1. PXD031891
     1. Label: PRIDE project
     2. Name: HIV-1 gp120 impairs spatial memory through CREB