Investigation of the roles of membrane lipid changes in Parkinson’s disease-associated microglia | Department of Biophysics and Cell Biology

A major cause of neuronal death in Parkinson's disease is the production of inflammatory cytokines by abnormally activated "disease-associated" microglia. In microglia, aggregated α-synuclein is known to trigger a signaling process that leads to increased expression and phosphorylation of the KV1.3 voltage-gated potassium channel, resulting in the production of inflammatory cytokines. Membrane lipid levels are also change in the disease, but these have not previously been linked to abnormal microglial functions. Recently, we have demonstrated that lipids can modulate the activation gating of KV1.3. However, much less is known about the effects of lipids on the KV1.3-related abnormal microglial functions in Parkinson's disease.
In our work, we aim to shed light on the direct connection between altered membrane lipid levels and pathological signaling of microglia in Parkinson's disease. Furthermore, our goal is to establish the principle of targeting high-affinity KV1.3 peptide inhibitors to the diseased cells, which may selectively inhibit neuronal death in Parkinson’s and potentially other neurodegenerative diseases as well.