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MiR-107 overexpression attenuates neurotoxicity induced by 6-hydroxydopamine both in vitro and in vivo

2019; Elsevier BV; Volume: 315; Linguagem: Inglês

10.1016/j.cbi.2019.108908

1872-7786

Li Sun, Tingting Zhang, Wenna Xiu, Wenhui Cao, Mengfei He, Wenqiang Sun, Weina Zhao,

Extracellular vesicles in disease

Alzheimer's disease (AD), the most common form of dementia, is a neurodegenerative disease characterized by neuronal atrophy in various brain regions. The expression of miR-107 is down-regulated in AD patients and target genes of miR-107 have been shown to directly involved in AD. In this study, we aimed to investigate the potential neuroprotective effects of miR-107. We first assessed brain activity in health controls and patients with AD. Then we examined miR-107 expression in SH-SY5Y and PC12 cells treated with 6-hydroxydopamine (6-OHDA), and investigated its function in cytotoxicity induced by 6-OHDA. We predicted a potential miR-107 target and assessed its role in miR-107 mediated effects and explored the intracellular signaling pathways downstream of miR-107. Finally, we assessed the function of miR-107 in the mouse model insulted by 6-OHDA. We found that 6-OHDA suppressed miR-107 expression and miR-107 played neuroprotective effects against 6-OHDA mediated cytotoxicity. We showed that miR-107 targeted programmed cell death 10 (PDCD10). MiR-107 suppressed PDCD10 expression and exogenous expression of PDCD10 inhibited miR-107 mediated neuroprotection. Additionally, we found that Notch signal pathway was downstream of miR-107/PDCD10. Finally, we found that 6-OHDA treatment suppressed miR-107 in mice and restoration of miR-107 alleviated motor disorder in the mouse model. Our study shows that miR-107 plays important neuroprotective roles against neurotoxicity both in vitro and in vivo by inhibiting PDCD10. Our findings confirm that miR-107 may be involved in AD pathogenesis and may be a therapeutic target for the treatment of AD-related impairments.