PXD041648 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2023-09-05 |
AnnouncementXML | Submission_2023-09-05_10:47:48.366.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | PhillipWilmarth |
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: schizophrenia, isobaric labeling, prefrontal cortex, mass spectrometry, lipid nanoparticle, personalized medicine,microRNA, quantitative proteomics, synaptic proteins |
Contact List
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 | |
PhillipWilmarth |
contact affiliation | OHSU |
contact email | wilmarth@ohsu.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD041648
- Label: PRIDE project
- Name: MicroRNA137-loaded lipid nanoparticles regulate synaptic proteins in the prefrontal cortex