PXD041648

PXD041648 is an original dataset announced via ProteomeXchange.

Title	MicroRNA137-loaded lipid nanoparticles regulate synaptic proteins in the prefrontal cortex
Description	Genome-wide association studies indicate allele variants in MIR137, the host gene of microRNA-137 (miR137), confer an increased risk of schizophrenia (SCZ). Expression of miR137 and its targets, many of which regulate synaptic functioning, are also associated with an increased risk of SCZ. As a result, miR137 represents an attractive target aimed at correcting the molecular basis for synaptic dysfunction in individuals with high genetic risk for SCZ. Advancements in nanotechnology utilize lipid nanoparticles (LNPs) to transport and deliver therapeutic RNA. However, there remains a gap in using LNPs to regulate gene and protein expression in the brain. To study the delivery of nucleic acids by LNPs to the brain, we found that LNPs released miR137 cargo and inhibited synaptic target transcripts in neuronal cultures. Biodistribution of LNPs loaded with firefly luciferase mRNA remained localized to the mouse prefrontal cortex (PFC) injection site without circulating to off-target organs. LNPs encapsulating Cre mRNA preferentially co-expressed in neuronal over microglial or astrocytic cells. Using quantitative proteomics, we found miR137 modulated glutamatergic synaptic protein networks that are commonly dysregulated in SCZ. These studies support engineering the next generation of brain-specific LNPs to deliver personalized RNA therapeutics and improve symptoms of central nervous system disorders.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:05:03.695.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-19 06:39:29	ID requested
1	2023-09-05 10:47:49	announced
⏵ 2	2023-11-14 09:05:13	announced	2023-11-14: Updated project metadata.

Palumbo MC, Gautam M, Sonneborn A, Kim K, Wilmarth PA, Reddy AP, Shi X, Marks DL, Sahay G, Abbas AI, Janowsky A, MicroRNA137-loaded lipid nanoparticles regulate synaptic proteins in the prefrontal cortex. Mol Ther, 31(10):2975-2990(2023) [pubmed]

submitter keyword: schizophrenia, isobaric labeling, prefrontal cortex, mass spectrometry, lipid nanoparticle, personalized medicine,microRNA, quantitative proteomics, synaptic proteins

Aaron Janowsky, Ph.D.
contact affiliation	Research Service (R&D22) VA Portland Health Care System 3710 SW US Veterans Hospital Rd. Portland, OR 97239 USA
contact email	janowsky@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.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/2023/09/PXD041648

PRIDE project URI

• PRIDE
  1. PXD041648
     1. Label: PRIDE project
     2. Name: MicroRNA137-loaded lipid nanoparticles regulate synaptic proteins in the prefrontal cortex