Evidence map›Paper›PMID 41888976›Full record

ArticleAlzheimer's research & therapy2026

A novel PGK1 activator improves Alzheimer's disease by regulating glycolysis.

Mei Li, Nianzhuang Qiu, Wenhui Niu, Chenliang Qian, Yuqiong Zhang, Wubin Yang, Fengyang Ding, Hao Wang, Xiaoyan Xu, Jie Xia and 1 more

Abstract read
In one paragraph

Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Mei Li *School of Pharmaceutical Sciences, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
Nianzhuang Qiu *School of Pharmaceutical Sciences, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
Wenhui Niu *School of Pharmaceutical Sciences, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
Chenliang QianState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Yuqiong ZhangSchool of Pharmaceutical Sciences, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
Wubin YangSchool of Pharmaceutical Sciences, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
Fengyang DingSchool of Pharmaceutical Sciences, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
Hao WangSchool of Pharmaceutical Sciences, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
Xiaoyan XuSchool of Pharmaceutical Sciences, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. xyxu@sdfmu.edu.cn.
Jie XiaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. jie.william.xia@hotmail.com.
Xuehui ZhangSchool of Pharmaceutical Sciences, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. zhangxuehui@sdfmu.edu.cn.

Funding

CAMS Innovation Fund for Medical Sciences 2021-I2M-1-069
6 · The paper itself

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the pathological accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles. Decreased glucose metabolism and ATP levels are well-established early biomarkers of AD. Recent studies indicate that the activation of phosphoglycerate kinase 1 (PGK1), a critical enzyme in the glycolytic pathway, promotes glucose metabolism and ATP production, thus offering potential therapeutic benefits for AD. However, two significant gaps persist: The expression pattern of PGK1 across different brain cell types remains unclear, and the structural diversity of known PGK1 activators is limited, restricting comprehensive investigation. In this study, we show that PGK1 exhibits high expression in neurons in the brain, and that reduced PGK1 expression is evident in both AβO-induced SH-SY5Y cells and 3×Tg-AD mice. PGK1 overexpression mitigates AβO-induced damage by enhancing glycolysis. Through surface plasmon resonance and molecular dynamics simulations, we identify compound L03 (Specs ID: AT-051/43421517) as a novel PGK1 activator. Pretreatment with compound L03 protects against AβO-induced glycolytic dysfunction in SH-SY5Y cells. Furthermore, administration of compound L03 ameliorates cognitive deficits, Aβ deposition, and Tau hyperphosphorylation in 3×Tg-AD mice. Our findings highlight PGK1 as a crucial regulator of neuronal bioenergetics in AD and position compound L03 as a promising PGK1 activator for restoring glycolytic function.

Indexed as

Alzheimer DiseaseGlycolysisPhosphoglycerate KinaseAmyloid beta-PeptidesAnimalsBrainCell Line, TumorDisease Models, AnimalHumansMiceMice, TransgenicNeuronsAmyloid beta-PeptidesPGK1 protein, humanPhosphoglycerate KinaseAlzheimer’s diseaseAβ depositionGlycolysisPhosphoglycerate kinase 1

Identifiers

PMID41888976
PMCPMC13141400

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.