Parkinson’s disease and other synucleinopathies cause an accumulation of a protein called α-Synuclein, which forms Lewy bodies and Lewy neurites. Lewy bodies are abnormal clusters of α-Synuclein that develop in the brain. As well as containing the disease hallmark α-Synuclein protein, Lewy Bodies also contain lipids.
Scientists identified a new therapeutic target, a triacylglycerol lipase, called LIPE, which affects lipid metabolism by breaking down TAGs. Reducing LIPE activity decreased α-Synuclein accumulation in round, membrane-rich cytoplasmic inclusions and decreased PD-associated phosphorylated α-Synuclein and insoluble α-Synuclein levels.
Targeting fatty acid metabolism through the lipid degradation pathway, particularly through the modulation of phospholipid-incorporated fatty acids, represents a promising strategy for treating synucleinopathies.
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