PXD055911-1

PXD055911 is an original dataset announced via ProteomeXchange.

Title	Targeting supramammillary circuits restores cognitive and noncognitive function in Alzheimer’s disease
Description	Although progressive cognitive decline is the hallmark symptom in Alzheimer’s disease (AD) patients, patients often develop noncognitive neuropsychiatric symptoms, such as anxiety and depression. The neural circuit basis for these different AD symptoms is poorly understood. Therapeutic strategies effectively targeting both cognitive and noncognitive symptoms in AD are largely lacking. Here we identified molecularly and functionally distinct supramammillary (SuM) subpopulations projecting to dorsal dentate gyrus (dDG) or ventral dentate gyrus (vDG), which differentially involved in memory and mood regulation. Interestingly, dDG- and vDG-projecting SuM neurons in AD model mice exhibited aberrant activity during cognitive and affective behaviors, respectively. Optogenetic activation of SuM-dDG or SuM-vDG pathways selectively rescued memory impairment and anxiety/depression-like behavioral deficits in AD mice. Furthermore, cross-species comparison of AD mouse and human phosphoproteomes revealed that SuM stimulation reversed pathological phosphorylation of mouse-to-human conserved proteins related to broad AD deficits. Thus, targeting SuM circuits may be an effective strategy for treating both cognitive and non-cognitive symptoms in AD patients.
HostingRepository	PRIDE
AnnounceDate	2025-09-25
AnnouncementXML	Submission_2025-09-25_11:14:14.085.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ling Xie
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-16 13:16:11	ID requested
⏵ 1	2025-09-25 11:14:14	announced

Dataset with its publication pending

submitter keyword: Alzheimer’s disease (AD), LC-MS

Juan Song
contact affiliation	Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
contact email	juansong@email.unc.edu
lab head
Ling Xie
contact affiliation	UNC at Chapel Hill
contact email	xiel@email.unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055911
     1. Label: PRIDE project
     2. Name: Targeting supramammillary circuits restores cognitive and noncognitive function in Alzheimer’s disease