Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress
The accumulation of α-synuclein (αSyn) has been implicated as a causal factor in the pathogenesis of Parkinson’s disease (PD). There is growing evidence that supports mitochondrial dysfunction as a potential primary cause of dopaminergic neuronal death in PD. Here, we focused on reciprocal interacti...
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MDPI AG
2021-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/2/110 |
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| author | Yifei Wang Yasuharu Shinoda An Cheng Ichiro Kawahata Kohji Fukunaga |
| author_facet | Yifei Wang Yasuharu Shinoda An Cheng Ichiro Kawahata Kohji Fukunaga |
| author_sort | Yifei Wang |
| collection | DOAJ |
| description | The accumulation of α-synuclein (αSyn) has been implicated as a causal factor in the pathogenesis of Parkinson’s disease (PD). There is growing evidence that supports mitochondrial dysfunction as a potential primary cause of dopaminergic neuronal death in PD. Here, we focused on reciprocal interactions between αSyn aggregation and mitochondrial injury induced by oxidative stress. We further investigated whether epidermal fatty acid-binding protein 5 (FABP5) is related to αSyn oligomerization/aggregation and subsequent disturbances in mitochondrial function in neuronal cells. In the presence of rotenone, a mitochondrial respiratory chain complex I inhibitor, co-overexpression of FABP5 with αSyn significantly decreased the viability of Neuro-2A cells compared to that of αSyn alone. Under these conditions, FABP5 co-localized with αSyn in the mitochondria, thereby reducing mitochondrial membrane potential. Furthermore, we confirmed that pharmacological inhibition of FABP5 by its ligand prevented αSyn accumulation in mitochondria, which led to cell death rescue. These results suggested that FABP5 is crucial for mitochondrial dysfunction related to αSyn oligomerization/aggregation in the mitochondria induced by oxidative stress in neurons. |
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| language | English |
| last_indexed | 2024-03-09T03:57:26Z |
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| spelling | doaj.art-55494dffe8b14927b02a2274354a05e82023-12-03T14:18:46ZengMDPI AGBiomedicines2227-90592021-01-019211010.3390/biomedicines9020110Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative StressYifei Wang0Yasuharu Shinoda1An Cheng2Ichiro Kawahata3Kohji Fukunaga4Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6–3 Aramaki-Aoba, Aoba-ku, Sendai 980-8578, JapanDepartment of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6–3 Aramaki-Aoba, Aoba-ku, Sendai 980-8578, JapanDepartment of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6–3 Aramaki-Aoba, Aoba-ku, Sendai 980-8578, JapanDepartment of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6–3 Aramaki-Aoba, Aoba-ku, Sendai 980-8578, JapanDepartment of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6–3 Aramaki-Aoba, Aoba-ku, Sendai 980-8578, JapanThe accumulation of α-synuclein (αSyn) has been implicated as a causal factor in the pathogenesis of Parkinson’s disease (PD). There is growing evidence that supports mitochondrial dysfunction as a potential primary cause of dopaminergic neuronal death in PD. Here, we focused on reciprocal interactions between αSyn aggregation and mitochondrial injury induced by oxidative stress. We further investigated whether epidermal fatty acid-binding protein 5 (FABP5) is related to αSyn oligomerization/aggregation and subsequent disturbances in mitochondrial function in neuronal cells. In the presence of rotenone, a mitochondrial respiratory chain complex I inhibitor, co-overexpression of FABP5 with αSyn significantly decreased the viability of Neuro-2A cells compared to that of αSyn alone. Under these conditions, FABP5 co-localized with αSyn in the mitochondria, thereby reducing mitochondrial membrane potential. Furthermore, we confirmed that pharmacological inhibition of FABP5 by its ligand prevented αSyn accumulation in mitochondria, which led to cell death rescue. These results suggested that FABP5 is crucial for mitochondrial dysfunction related to αSyn oligomerization/aggregation in the mitochondria induced by oxidative stress in neurons.https://www.mdpi.com/2227-9059/9/2/110α-SynucleinFABP5aggregationmitochondriaParkinson’s disease |
| spellingShingle | Yifei Wang Yasuharu Shinoda An Cheng Ichiro Kawahata Kohji Fukunaga Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress Biomedicines α-Synuclein FABP5 aggregation mitochondria Parkinson’s disease |
| title | Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress |
| title_full | Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress |
| title_fullStr | Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress |
| title_full_unstemmed | Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress |
| title_short | Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress |
| title_sort | epidermal fatty acid binding protein 5 fabp5 involvement in alpha synuclein induced mitochondrial injury under oxidative stress |
| topic | α-Synuclein FABP5 aggregation mitochondria Parkinson’s disease |
| url | https://www.mdpi.com/2227-9059/9/2/110 |
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