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Retinoic Acid Prevents α-Synuclein Preformed Fibrils-Induced Toxicity via Inhibiting STAT1-PARP1 Signaling

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Abstract

Parkinson's disease (PD), the second-most prevalent neurodegenerative disorder, is characterized by the aberrant deposition of α-synuclein (α-Syn) aggregation in neurons. Recent reports have shown that retinoic acid (RA) ameliorates motor deficits. However, the underlying molecular mechanisms remain unclear. In this article, we investigated the effects of RA on cellular and animal models of PD. We found that RA is beneficial for neuronal survival in PD-associated models. In α-Syn preformed fibrils-treated mice, RA administration relieved the formation of intracellular inclusions, dopaminergic neuronal loss, and behavioral deficits. α-Syn preformed fibrils-treated SH-SY5Y cells manifested decreased cell viability, apoptosis, α-Syn aggregation, and autophagy defects. All these negative phenomena were alleviated by RA. More importantly, RA could inhibit the neurotoxicity via inhibiting α-Syn preformed fibrils-induced STAT1-PARP1 signaling, which could also be antagonized by IFN-γ. In conclusion, RA could hinder α-Syn preformed fibrils-induced toxicity by inhibiting STAT1-PARP1 signaling. Thus, we present new insight into RA in PD management.

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The authors declare that all data supporting the findings of this study are available within the article.

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Acknowledgements

This study is supported by the Natural Science Foundation of Hubei Province (2020CFB737) and the Medical Science and Technology Development Program of Shandong Province (No. 202003081484).

Funding

This work was supported by the Natural Science Foundation of Hubei Province (No. 2020CFB737) to Xiang Gao, and the Medical and Health Development Project of Shandong Province (No. 202003081484) to Zengxia Ma.

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Authors and Affiliations

  1. Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Lingyan Zhou

  2. Department of Pulmonary and Critical Care Medicine, Shandong Public Health Clinical Center, Jinan, 250013, China

    Zengxia Ma

  3. Central Laboratory, Scientific Research Department, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Xiang Gao

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  1. Lingyan Zhou
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G.X. and M.Z. provided funding and supervision and reviewed and edited the manuscript. Z.L. designed and performed experiments, analyzed the data, and wrote the manuscript. All authors have read and approved the submitted version.

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Correspondence to Zengxia Ma or Xiang Gao.

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The Declaration of Helsinki and guidelines of Renmin Hospital, Wuhan University. was strictly followed during animal maintenance and experiments. The Animal Care and Use Committee of Renmin Hospital of Wuhan University reviewed and approved the protocol (20211104).

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Zhou, L., Ma, Z. & Gao, X. Retinoic Acid Prevents α-Synuclein Preformed Fibrils-Induced Toxicity via Inhibiting STAT1-PARP1 Signaling. Mol Neurobiol 60, 4828–4841 (2023). https://doi.org/10.1007/s12035-023-03376-x

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