Evidence map›Paper›PMID 40301979›Full record

ArticleAlzheimer's research & therapy2025

The autocrine motility factor receptor delays the pathological progression of Alzheimer's disease via regulating the ubiquitination-mediated degradation of APP.

Jingjing Zhang, Congcong Liu, Jing Liu, Yuting Cui, Yuli Hou, Qiao Song, Xiaomin Zhang, Xiaoling Wang, Qian Zhang, Min Cao and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Jingjing ZhangDepartment and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China.
Congcong LiuDepartment and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China.
Jing LiuDepartment and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China.
Yuting CuiDepartment and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China.
Yuli HouDepartment and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China.
Qiao SongDepartment and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China.
Xiaomin ZhangDepartment and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China.
Xiaoling WangDepartment and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China.
Qian ZhangDepartment and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China.
Min CaoDepartment of Clinical Laboratory, Beijing Huairou Hospital, Beijing, 101400, China.
Wenchao WangDepartment and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China.
Peichang Wang *Department and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China. pcw1905@126.com.
Yaqi Wang *Department and Institute of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, 100053, China. wangyaqi0619@163.com.

Funding

Beijing Hospital Authority Youth Program QML20230812National Natural Science Foundation of China 81871714National Natural Science Foundation of China 82102487Research and Development Foundation of Capital Medical University PYZ23052the State Key Program of National Natural Science Foundation of China 82030064
6 · The paper itself

Abstract

backgroundThe ubiquitin-proteasome system (UPS) is responsible for most protein degradation and its malfunction is normally observed in neurodegenerative diseases, including Alzheimer's disease (AD). The autocrine motility factor receptor (AMFR) is an E3 ubiquitin ligase that resides on the endoplasmic reticulum membrane and is involved in various essential biological processes. However, the role of AMFR in AD is still unidentified.

methodsBehavioral experiments, including open-field test (OFT), novel object recognition test (NORT) and morris water maze test (MWMT) were conducted after adeno-associated virus (AAV) microinjection into AD model mice. Western blot, co-immunoprecipitation (Co-IP), qPCR and ubiquitination assay were used to analyze AMFR mediated ubiquitination degradation of amyloid precursor protein (APP). ELISA was employed to evaluate changes in amyloidogenic cleavage products of APP following upregulation or downregulation of AMFR in neural cells and analyze AMFR levels in serum and cerebrospinal fluid (CSF) of AD patients.

resultsThe progressive decline in AMFR levels was found not only in the hippocampus of APPswe/PSEN1dE9 (APP/PS1) mice but also in the CSF and serum of patients with AD. Moreover, the interaction of AMFR and APP was observed both in hippocampal tissues and brain neurons. In addition, AMFR promoted the K11-linked polyubiquitination of APP to speed up its proteasomal degradation, resulting in decreased Aβ production. Importantly, AMFR overexpression largely rescued the cognitive and synaptic deficits in APP/PS1 mice.

conclusionsTaken together, our results demonstrated that AMFR reduced Aβ production and alleviated cognitive impairment by promoting the ubiquitination-mediated degradation of APP. This study indicated that AMFR could have the potential to be a therapeutic target of early-stage AD.

Indexed as

Alzheimer DiseaseAmyloid beta-Protein PrecursorReceptors, Autocrine Motility FactorUbiquitinationAnimalsDisease Models, AnimalDisease ProgressionFemaleHippocampusHumansMaleMiceMice, Inbred C57BLMice, TransgenicProteolysisAMFR protein, humanAmyloid beta-Protein PrecursorReceptors, Autocrine Motility FactorAlzheimer’s diseaseAmyloid precursor proteinAutocrine motility factor receptorE3 ubiquitin ligaseUbiquitination

Identifiers

PMID40301979
PMCPMC12039061

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.