Evidence map›Paper›PMID 40135564›Full record

ArticleCNS neuroscience & therapeutics2025

Inhibition of Salt-Inducible Kinase 2 Protects Motor Neurons From Degeneration in ALS by Activating Autophagic Flux and Enhancing mTORC1 Activity.

Weiwei Liang, Chunting Zhang, Di Wang, Xiaoli Su, Xingli Tan, Yueqing Yang, Chaohua Cong, Ying Wang, Di Huo, Hongyong Wang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
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

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

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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

1 citing paper in PubMed.

  1. Article
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

13 authors.

Weiwei LiangDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Chunting ZhangDivision of Life Science and Technology of China, Department of Neurology, The First Affiliated Hospital of USTC, Hefei, P.R. China.
Di WangDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Xiaoli SuDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Xingli TanDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Yueqing YangDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Chaohua CongDepartment of Neurology, Shanghai No. 9 People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Ying WangDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Di HuoDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Hongyong WangDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Shuyu WangDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Xudong WangDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Honglin FengDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.ORCID 0000-0002-5062-8846

Funding

Innovative Scientific Research Fund of Harbin Medical University 2023-KYYWF-0195National Natural Science Foundation of China 82271450National Natural Science Foundation of China 82301599
6 · The paper itself

Abstract

objectivesAutophagic impairment has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Salt-inducible kinase 2 (SIK2), a member of the AMP-activated protein kinase (AMPK) family widely expressed in the central nervous system, plays critical roles in neuronal survival, neurogenesis, and the regulation of autophagy. This study aims to investigate the effects and underlying mechanisms of SIK2 in the pathogenesis of ALS.

methodsIn our work, we used both in vivo and in vitro models of ALS to study the effect of SIK2. Protein and RNA levels were assessed by Western blot, RT-qPCR, immunofluorescence, and immunohistochemistry. Cell viability and apoptosis were evaluated using CCK-8 assay and flow cytometry. Transmission electron microscopy was employed to examine autophagic vacuoles. Additionally, lentivirus particles carrying shRNA targeting SIK2 (sh-SIK2) were injected into the lateral ventricle of ALS mice at 60 days of age. Motor performance was evaluated by the rotarod test.

resultsWe observed that increased expression of SIK2 significantly contributed to the degeneration of motor neurons in both the cellular model and the hSOD1

conclusionsOur findings reveal that SIK2 regulates autophagic flux by modulating lysosomal acidification, thereby influencing the degradation of mutant SOD1 aggregates. SIK2 suppression enhances autophagy-mediated clearance of toxic protein aggregates and protects motor neurons, highlighting its potential as a therapeutic target for ALS.

Indexed as

Amyotrophic Lateral SclerosisAutophagyMechanistic Target of Rapamycin Complex 1Motor NeuronsNerve DegenerationProtein Serine-Threonine KinasesAnimalsHumansMaleMiceMice, Inbred C57BLMice, TransgenicMechanistic Target of Rapamycin Complex 1Protein Serine-Threonine Kinasessalt-inducible kinase-2, humansalt-inducible kinase-2, mouseamyotrophic lateral sclerosisautophagyCu/Zn superoxide dismutasemTORC1salt‐inducible kinase 2

Identifiers

PMID40135564
PMCPMC11937914

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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.