Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress

The accumulation of alpha-synuclein (alpha Syn) 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 alpha Syn aggregation and mitochondrial injury induced by oxidative stress. We further investigated whether epidermal fatty acid-binding protein 5 (FABP5) is related to alpha Syn oligomerization/aggregation and subsequent disturbances in mitochondrial function in neuronal cells. In the presence of rotenone, a mitochondrial respiratory chain complex I inhibitor, cooverexpression of FABP5 with alpha Syn significantly decreased the viability of Neuro-2A cells compared to that of alpha Syn alone. Under these conditions, FABP5 alpha-localized with alpha Syn in the mitochondria, thereby reducing mitochondrial membrane potential. Furthermore, we confirmed that pharmacological inhibition of FABP5 by its ligand prevented alpha Syn accumulation in mitochondria, which led to cell death rescue. These results suggested that FABP5 is crucial for mitochondrial dysfunction related to alpha Syn oligomerization/aggregation in the mitochondria induced by oxidative stress in neurons.

Automated summary

The research revealed that the interaction between FABP5 and α Syn can lead to mitochondrial dysfunction in neuronal cells, increasing the risk of PD development.