Evidence map›Paper›PMID 42015299›Full record

ArticleTranslational neurodegeneration2026

NDST3 suppression restores lysosomal acidification and ameliorates amyloid-β and MAPT/tau pathology in Alzheimer's disease.

Chuanhua Ge, Kun Wang, Huiyuan Tang, Yiling Ke, Huai Wang, Qiang Fu, Yun Xiu, Yongzheng Guo, Yun-Fang Jia, Zhimin Long and 2 more

Abstract read
In one paragraph

Article in Translational neurodegeneration, 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
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1 · What the graph read from it

What it found

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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

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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

12 authors.

Chuanhua GeCenter for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, No.1 YiXueYuan Road, YuZhong District, Chongqing, 400016, China.
Kun WangCenter for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, No.1 YiXueYuan Road, YuZhong District, Chongqing, 400016, China.
Huiyuan TangCenter for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, No.1 YiXueYuan Road, YuZhong District, Chongqing, 400016, China.
Yiling KeCenter for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, No.1 YiXueYuan Road, YuZhong District, Chongqing, 400016, China.
Huai WangCenter for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, No.1 YiXueYuan Road, YuZhong District, Chongqing, 400016, China.
Qiang FuCenter for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, No.1 YiXueYuan Road, YuZhong District, Chongqing, 400016, China.
Yun XiuKey Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing Medical University, No.1 YiXueYuan Road, YuZhong District, Chongqing, 400016, China.
Yongzheng GuoDivision of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Yun-Fang JiaCenter for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, No.1 YiXueYuan Road, YuZhong District, Chongqing, 400016, China.
Zhimin LongCenter for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, No.1 YiXueYuan Road, YuZhong District, Chongqing, 400016, China.
Guiqiong HeCenter for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, No.1 YiXueYuan Road, YuZhong District, Chongqing, 400016, China. guiqionghe@cqmu.edu.cn.
Qing TangCenter for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, No.1 YiXueYuan Road, YuZhong District, Chongqing, 400016, China. tangqingzoe@cqmu.edu.cn.

Funding

National Natural Science Foundation of China 82201582National Natural Science Foundation of China 82371203Natural Science Foundation of Chongqing, China CSTB2024NSCQ-MSX0483Program for Youth Innovation in Future Medicine, Chongqing Medical University W0168Project of the Top-Notch Talent Cultivation Program for the Graduate Students of Chongqing Medical University BJRC202310Science and Technology Research Program of Chongqing Municipal Education Commission KJQN202200457
6 · The paper itself

Abstract

backgroundImpairment of lysosomal acidification has recently been identified as a critical driver of amyloid-β and MAPT/tau pathology in Alzheimer's disease (AD). Restoring lysosomal acidification is a promising strategy for AD treatment. N-deacetylase and N-sulfotransferase 3 (NDST3) is a newly discovered tubulin deacetylase that regulates lysosomal acidification by influencing the recruitment of V-ATPase V1 subunits to lysosomes. Nevertheless, the role of NDST3 in AD remains entirely unexplored.

methodsWe began by comparing the effects of NDST3 and histone deacetylase 6 (HDAC6), a well-known tubulin deacetylase with established roles in AD, on lysosomal acidification. Using HT22 cell-based models of AD, we knocked down NDST3 to examine its role in lysosomal acidification and degradative function in the context of this disease. We also evaluated the expression profile of NDST3 in both in vitro and in vivo models of AD. Finally, we investigated the consequences of NDST3 suppression on lysosomal acidity and related AD pathological features in the hippocampi of 3 × Tg-AD mice.

resultsNDST3 differs from HDAC6 in the subcellular spatial patterns of catalyzing microtubule deacetylation but parallels HDAC6 in regulating lysosomal pH. In HT22 cells with APP695

conclusionsOur study identified NDST3 as a key factor regulating lysosomal acidity in AD. Suppressing NDST3 restores lysosomal function in AD and protects against AD pathology, highlighting NDST3 as a promising therapeutic target for AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesLysosomestau ProteinsAnimalsHippocampusHistone Deacetylase 6HumansHydrogen-Ion ConcentrationMiceMice, TransgenicAmyloid beta-PeptidesHistone Deacetylase 6tau ProteinsAlzheimer's diseaseAmyloid plaqueHistone deacetylase 6Lysosomal acidificationMAPT/tauN-deacetylase and N-sulfotransferase 3

Identifiers

PMID42015299
PMCPMC13097816

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.