Olfactory mucosal mesenchymal stem cell-derived exosome Lnc A2M-AS1 ameliorates oxidative stress by regulating TP53INP1-mediated mitochondrial autophagy through interacting with IGF2BP1 in Parkinson's diseases

  • Cell Biol Toxicol. 2025 Mar 20;41(1):60. doi: 10.1007/s10565-025-10009-7.
Jiangshan Zhang  1 ,  Chuang Wang  2 ,  Guoshuai Yang  1 ,  Yanhui Zhou  1 ,  Dan Hou  1 ,  Ying Xia  3
Affiliations
  • 1. Department of Neurology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, 570208, Hainan Province, People's Republic of China.
  • 2. Department of Neurosurgery, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, No.43, Renmin Avenue, Meilan District, Haikou, 570208, Hainan Province, People's Republic of China.
  • 3. Department of Neurosurgery, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, No.43, Renmin Avenue, Meilan District, Haikou, 570208, Hainan Province, People's Republic of China. [email protected].
PMID: 40111649 DOI: 10.1007/s10565-025-10009-7
Abstract

Background: Exosome Lnc A2M-AS1 from olfactory mucosa mesenchymal stem cells (OM-MSCs) can ameliorate oxidative stress by improving Mitophagy in cardiomuscular cells; however, it remains unclear whether this effect exists in the brain tissues of patients with Parkinson's Disease (PD).

Methods: OM-MSC-Exosomes were isolated and verified based on morphology and specific biomarkers. The effects of OM-MSC-Exo on mitochondrial Autophagy, oxidative stress, and lncRNA A2M-AS1 were detected in MPP+-treated HT22 cells. The effects of OM-MSC-Exos on mitochondrial Autophagy and oxidative stress were detected in an MPTP-induced Parkinson's Disease (PD) model in C57BL/6 mice. The interaction between IGF2BP1, A2M-AS1, and TP53INP1 was assessed via RNA pull-down/RNA Immunoprecipitation and RNA stability assays. The effects of lnc A2M-AS1 on IGF2BP1/TP53INP1-mediated mitochondrial Autophagy and oxidative stress were verified in MPP+-treated HT22 cells and MPTP-induced PD mouse models.

Results: Exosomes isolated from olfactory mucosa mesenchymal stem cells were found to be rich in Lnc A2M-AS1. Lnc A2M-AS1 was proved to be able to ameliorate oxidative stress induced by MPP+ in HT22 cells. lncRNA A2M-AS1 regulates oxidative stress by enhancing Mitophagy in HT22 cells. In addition, lncRNA A2M-AS1 induced Mitophagy through TP53INP1 and mediated TP53INP1 expression by binding to IGF2BP1. Furthermore, OM-MSC-Exo and Lnc A2M-AS1 treatment improved symptoms and ameliorated oxidative stress in MPTP-induced PD mouse models.

Conclusion: Collectively, lncRNA A2M-AS1 from OM-MSC-derived Exosomes regulates TP53INP1 expression by targeting IGF2BP1 to induce Mitophagy and ameliorate oxidative stress. OM-MSC-derived Exosomes could potentially serve as promising candidates for new treatment methods for PD.

Keywords
Exosome; Lnc A2M-AS1; Mitophagy; Olfactory Mucosa Mesenchymal Stem Cell; Oxidative Stress; Parkinson’s Disease.
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