10.3389/fnins.2018.00397.s003
Xiaojuan Han
Xiaojuan
Han
Jialei Zhu
Jialei
Zhu
Xinlei Zhang
Xinlei
Zhang
Qiqi Song
Qiqi
Song
Jianhua Ding
Jianhua
Ding
Ming Lu
Ming
Lu
Sifan Sun
Sifan
Sun
Gang Hu
Gang
Hu
Data_Sheet_3_Plin4-Dependent Lipid Droplets Hamper Neuronal Mitophagy in the MPTP/p-Induced Mouse Model of Parkinson’s Disease.XLS
Frontiers
2018
Plin4
lipid droplets
Parkinson’s disease
DA neurons
mitophagy
2018-06-18 04:17:07
Dataset
https://frontiersin.figshare.com/articles/dataset/Data_Sheet_3_Plin4-Dependent_Lipid_Droplets_Hamper_Neuronal_Mitophagy_in_the_MPTP_p-Induced_Mouse_Model_of_Parkinson_s_Disease_XLS/6570809
<p>Epidemiological studies have shown that both lipid metabolism disorder and mitochondrial dysfunction are correlated with the pathogenesis of neurodegenerative diseases (NDDs), including Parkinson’s disease (PD). Emerging evidence suggests that deposition of intracellular lipid droplets (LDs) participates in lipotoxicity and precedes neurodegeneration. Perilipin family members were recognized to facilitate LD movement and cellular signaling interactions. However, the direct interaction between Perilipin-regulated LD deposition and mitochondrial dysfunction in dopaminergic (DA) neurons remains obscure. Here, we demonstrate a novel type of lipid dysregulation involved in PD progression as evidenced by upregulated expression of Plin4 (a coating protein and regulator of LDs), and increased intracellular LD deposition that correlated with the loss of TH-ir (Tyrosine hydroxylase-immunoreactive) neurons in the MPTP/p-induced PD model mouse mesencephalon. Further, in vitro experiments showed that inhibition of LD storage by downregulating Plin4 promoted survival of SH-SY5Y cells. Mechanistically, reduced LD storage restored autophagy, leading to alleviation of mitochondrial damage, which in turn promoted cell survival. Moreover, the parkin-poly-Ub-p62 pathway was involved in this Plin4/LD-induced inhibition of mitophagy. These findings were further confirmed in primary cultures of DA-nergic neurons, in which autophagy inhibitor treatment significantly countermanded the ameliorations conferred by Plin4 silencing. Collectively, these experiments demonstrate that a dysfunctional Plin4/LD/mitophagy axis is involved in PD pathology and suggest Plin4-LDs as a potential biomarker as well as therapeutic strategy for PD.</p>