Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the Caenorhabditis elegans Model.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Neuroblastoma* ; Neurotoxicity Syndromes* ; Parkinson Disease* ; MicroRNAs*/genetics; Humans ; Animals ; Oxidopamine/pharmacology ; Caenorhabditis elegans ; alpha-Synuclein ; Beclin-1 ; Sirtuin 1/genetics ; Autophagy

Defective autophagy is one of the cellular hallmarks of Parkinson's disease (PD). Therefore, a therapeutic strategy could be a modest enhancement of autophagic activity in dopamine (DA) neurons to deal with the clearance of damaged mitochondria and abnormal protein aggregates. Syringin (SRG) is a phenolic glycoside derived from the root of Acanthopanax senticosus . It has antioxidant, anti-apoptotic, and anti-inflammatory properties. However, whether it has a preventive effect on PD remains unclear. The present study found that SRG reversed the increase in intracellular ROS-caused apoptosis in SH-SY5Y cells induced by neurotoxin 6-OHDA exposure. Likewise, in C. elegans, degeneration of DA neurons, DA-related food-sensitive behaviors, longevity, and accumulation of α-synuclein were also improved. Studies of neuroprotective mechanisms have shown that SRG can reverse the suppressed expression of SIRT1, Beclin-1, and other autophagy markers in 6-OHDA-exposed cells. Thus, these enhanced the formation of autophagic vacuoles and autophagy activity. This protective effect can be blocked by pretreatment with wortmannin (an autophagosome formation blocker) and bafilomycin A1 (an autophagosome-lysosome fusion blocker). In addition, 6-OHDA increases the acetylation of Beclin-1, leading to its inactivation. SRG can induce the expression of SIRT1 and promote the deacetylation of Beclin-1. Finally, we found that SRG reduced the 6-OHDA-induced expression of miR-34a targeting SIRT1 . The overexpression of miR-34a mimic abolishes the neuroprotective ability of SRG. In conclusion, SRG induces autophagy via partially regulating the miR-34a/SIRT1/Beclin-1 axis to prevent 6-OHDA-induced apoptosis and α-synuclein accumulation. SRG has the opportunity to be established as a candidate agent for the prevention and cure of PD.

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Keywords: 6-hydroxydopamine (6-OHDA); Beclin-1; C. elegans; Parkinson’s disease; SH-SY5Y cells; SIRT1; autophagy; miR-34a; syringin; α-synuclein

8HW4YBZ748 (Oxidopamine)
I6F5B11C96 (syringin)
0 (alpha-Synuclein)
0 (Beclin-1)
EC 3.5.1.- (Sirtuin 1)
0 (MicroRNAs)
EC 3.5.1.- (SIRT1 protein, human)

Date Created: 20230928 Date Completed: 20230929 Latest Revision: 20230930

20230930

PMC10527269

10.3390/cells12182310

37759532