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Autophagy in Multiple Sclerosis: Phagocytosis and Autophagy of Oligodendrocyte Precursor Cells

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Abstract  

Multiple sclerosis (MS) is a leading cause of chronic neurological dysfunction in young to middle-aged adults, affecting approximately 2.5 million people worldwide. It is characterized by inflammation, multifocal demyelination, axonal loss, and white and gray matter gliosis. Autophagy is a highly conserved protein degradation pathway. Polymorphisms in autophagy-related genes have been implicated in a variety of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, psoriasis and MS. However, the significance of autophagy in MS remains to be elucidated. This paper aims to explore the potential role of autophagy-related genes in MS diseases by using bioinformatics combined with machine learning methods. Finally, we obtained 9 autophagy genes with the highest correlation with MS, and further changes in these autophagy genes were verified in the experimental autoimmune encephalomyelitis (EAE) model and oligodendrocyte precursor cells (OPCs) engulfed myelin debris (MD). Combined with bioinformatic analysis and experimental data, Becn1 showed obvious expression abnormalities suggesting that this gene has vital functions in autophagy and MD engulfed by OPCs. This work will be of great significance for the further exploration of autophagy-related genes in demyelinating diseases.

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Data and Code Availability

This study analyzed publicly available data sets. These data can be found here: GSE131282, GSE135511 and GSE150562 were downloaded from the NCBI GEO database (https://www.ncbi.nlm.nih.gov/geo/). Any additional information may be provided upon reasonable request.

Abbreviations

Pdgfrα:

Platelet-derived growth factor receptor α

Ng2:

Glial antigen 2

Becn1:

Beclin 1

Napsa:

Napsin A aspartic peptidase

Atm:

Ataxia telangiectasia mutated

Itgam:

Integrin alpha M

Src:

Rous sarcoma oncogene

Ntrk2:

Neurotrophic tyrosine kinase, receptor, type 2

Fgfr2:

Fibroblast growth factor receptor 2

Rab10:

Member RAS oncogene family

Atg5:

Autophagy related 5

Plk3c3:

Phosphatidylinositol 3-kinase catalytic subunit type 3

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Acknowledgements

This study was supported by the Chinese National Natural Science Foundation (Grant Nos. 82271199, 31970771, 82071396), the Shaanxi Provincial Key R&D Foundation (Grant No. 2021ZDLSF03-09), the Fundamental Research Funds for the Central Universities (Grant Nos.GK202201013, GK202202006, LHRCCX23177).

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Author notes

  1. Jia-Qi Wang and Qiang Li are contributed equally to this work.

Authors and Affiliations

  1. National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University), The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi’an, China

    Jia-Qi Wang, Jia-Yi He, Fang Zhou, Zi-Hao Huang, Yuan Zhang & Xing Li

  2. College of Urban and Environmental Sciences, Northwest University, Xi’an, China

    Qiang Li

  3. The Nervous System Disease Diagnosis and Treatment Engineering Technology Research Center of Ningxia, Yinchuan, 750001, China

    Li-Bin Wang

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Contributions

J.W. and Q.L. acquisition and interpretation of data. X.L. and Y.Z. participated in the conception and revision of the article. J.W., Q.L., J.H., F.Z. and Z.H. collated literatures. J.W. and Q.L. wrote the manuscript and made diagrams with feedback from all authors. X.L. and Y.Z. co-supervised the study and revised the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xing Li.

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Wang, JQ., Li, Q., He, JY. et al. Autophagy in Multiple Sclerosis: Phagocytosis and Autophagy of Oligodendrocyte Precursor Cells. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-03996-x

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