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Perilipin 4 Protein: an Impending Target for Amyotrophic Lateral Sclerosis

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Abstract

The pathogenesis of amyotrophic lateral sclerosis (ALS) might exist some relationships with the abnormal lipidomic metabolisms. Therefore, we observed and analyzed the alteration of perilipin 4 (PLIN 4) distribution in the anterior horns (AH); the central canals (CC) and its surrounding gray matter; the posterior horns (PH); and the anterior, lateral, and posterior funiculus (AF, LF, and PF) of the cervical, thoracic, and lumbar segments, as well as the alteration of PLIN 4 expression in the entire spinal cords at the pre-onset, onset, and progression stages of Tg(SOD1*G93A)1Gur (TG) mice and the same period of wild-type(WT) by fluorescent immunohistochemistry, the Western blot, and the image analysis. Results showed that the PLIN 4 distributions in the spinal AH, CC and its surrounding gray matter, PH, AF, and PF of the cervical, thoracic, and lumbar segments in the TG mice at the pre-onset, onset, and progression stages significantly increased compared with those at the same periods of WT mice; the gray matter was especially significant. No significant changes were detected in the LF. PLIN 4 extensively distributed in the neurons and the proliferation neural cells. The PLIN 4 distributions significantly gradually increased from the pre-onset to onset to progression stages, and significantly correlated with the gradual increase death of neural cells. Total PLIN 4 expression in the spinal cords of TG mice significantly increased from the pre-onset, to onset, and to progression stages compared with that in the WT mice. Our data suggested that the PLIN 4 distribution and expression alterations might participate in the death of neural cells in the pathogenesis of ALS through modulating the lipidomic metabolisms and the neural cell proliferation.

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Acknowledgments

The authors would like to thank the National Natural Science Foundation of China (30560042, 81160161, and 81360198), the Education Department of Jiangxi Province (GJJ170042, GJJ13198, GJJ170021), the Jiangxi Provincial Department of Science and Technology ([2014]-47, 20142BBG70062, 20171BAB215022), and the Health and Family Planning Commission of Jiangxi province (20181019) for supporting this study.

Funding

This research was supported by the National Natural Science Foundation of China (30560042, 81160161, and 81360198), the Education Department of Jiangxi Province (GJJ170042, GJJ13198, GJJ170021), the Jiangxi Provincial Department of Science and Technology ([2014]-47, 20142BBG70062, 20171BAB215022), and the Health and Family Planning Commission of Jiangxi province (20181019).

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  1. Lei Zhu, Fan Hu and Cheng Li contributed equally to this work.

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  1. Department of Neurology, Jiangxi Provincial People’s Hospital, Affiliated People’s Hospital of Nanchang University, Nanchang, China

    Lei Zhu, Fan Hu, Cheng Li, Caixiang Zhang, Ruiwen Hang & Renshi Xu

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Correspondence to Renshi Xu.

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Animal experiments were approved by the Animal Experiment Committee of the Animal Management Committee of Jiangxi Provincial People’s Hospital and Affiliated People’s Hospital of Nanchang University and were performed in accordance with the Guidelines for Animal Experiments at the Animal Management Committee of Jiangxi Provincial People’s Hospital and Affiliated People’s Hospital of Nanchang University.

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Zhu, L., Hu, F., Li, C. et al. Perilipin 4 Protein: an Impending Target for Amyotrophic Lateral Sclerosis. Mol Neurobiol 58, 1723–1737 (2021). https://doi.org/10.1007/s12035-020-02217-5

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