FABP5-binding lipids regulate autophagy in differentiated SH-SY5Y cells

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Parkinson's disease (PD) motor symptoms stem from dopaminergic neuron loss in the substantia nigra.
• Autophagy dysfunction is closely linked to Parkinson's disease pathogenesis.
• Lipid regulation of autophagy remains understudied compared to protein effectors.

Purpose of the Study:

• To identify endogenous lipid signaling molecules that modulate autophagy in dopaminergic-like cells.
• To investigate the role of fatty acid-binding protein 5 (FABP5) in autophagy regulation.
• To explore potential therapeutic targets for Parkinson's disease.

Main Methods:

• Differentiated SH-SY5Y cells, a dopaminergic neuron model, were used.
• FABP5 was knocked down to assess its effect on autophagy.
• Lipidomic screening identified FABP5-interacting lipids.
• RNA-sequencing (RNA-Seq) analyzed molecular mechanisms of lipid-induced autophagy inhibition.

Main Results:

• FABP5 knockdown suppressed autophagy in SH-SY5Y cells.
• 5-oxo-eicosatetraenoic acid (5OE), arachidonic acid (AA), stearic acid (SA), hydroxystearic acid (HSA), and palmitic acid (PA) were identified as FABP5-interacting lipids.
• 5OE, SA, and HSA potently inhibited autophagy, while AA and PA did not.
• RNA-Seq revealed shared and distinct signaling pathways affected by these lipids.

Conclusions:

• Specific lipids, including 5OE, SA, and HSA, can inhibit autophagy in dopaminergic-like cells.
• FABP5 plays a role in modulating autophagy, potentially through interacting lipids.
• These lipids and their pathways represent novel therapeutic targets for Parkinson's disease.