PXD063971-1

PXD063971 is an original dataset announced via ProteomeXchange.

Title	The raw proteomic data of overexpressing hCDK3 in neuron
Description	The neuronal loss induced-brain atrophy is the direct cause of Alzheimer’s disease (AD), but hardly can be observed in rodent AD models, and the underlying mechanisms remain unclear. Cell cycle reentry induces post-mitotic neuronal death (CRND). Here, we found that Cyclin dependent kinase 3 (CDK3) which drives cell cycle re-entry from G0 to G1 phase transition highly expresses in AD patients’ brain, and positively correlates with AD Braak stage and frontal atrophy. However, most of the rodent laboratory mouse lines have a stop-code mutation in Cdk3 gene. We generated neuronal specifically human CDK3 overexpression transgenic mice and the premature termination codon mutation correction knock-in mice (Cdk3(561DM)), and crossed them with two classic AD mouse models: 5xFAD and Tau-PS19 mice. Exogenous hCDK3 or endogenous mCdk3 expression both induced massive neuronal death and hippocampal atrophy, accompanying with exacerbated impairments of LTP and cognition in AD mice. We also screened and developed a CDK3 kinase inhibitor BMX330, which alleviated neuronal death and cognitive impairments in hCDK3-overexpressed mice. The multi proteomics and phosphoproteomics analyses of hCDK3 substrates further revealed that the CRND and synaptic dysfunctions are involved in CDK3 mediated neuronal loss. Our finding not only provide new evidence on the neuronal death mechanism of AD, but also created new AD mouse models which exhibit comprehensive AD-relevant pathological characteristics, particularly, neuronal death and brain atrophy. They may serve as useful tools in facilitating both AD research and drug discovery.
HostingRepository	PRIDE
AnnounceDate	2025-10-27
AnnouncementXML	Submission_2025-10-27_02:34:45.695.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shuzhong Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-15 04:39:38	ID requested
⏵ 1	2025-10-27 02:34:46	announced

Dataset with its publication pending

submitter keyword: neuronal death, Neuronal cell cycle re-entry,Alzheimer’s disease, CDK3.

Jie Zhang
contact affiliation	Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience,School of Medicine, Xiamen University, Xiangan South Road, Xiamen, Fujian, 361102 P. R. China
contact email	jiezhang@xmu.edu.cn
lab head
Shuzhong Wang
contact affiliation	Xiamen University
contact email	wangsz11@hotmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063971
     1. Label: PRIDE project
     2. Name: The raw proteomic data of overexpressing hCDK3 in neuron