Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. Inflammasome components are up-regulated in patients with PD.
  • Fig. S2. Inflammasome components are up-regulated, and activation occurs via NLRP3 in the 6-OHDA mouse model of PD.
  • Fig. S3. NLRP3 and ASC are up-regulated in the MitoPark mouse model of PD.
  • Fig. S4. NLRP3 is expressed by microglia in the α-synuclein PFF mouse model.
  • Fig. S5. Validation of α-synuclein PFFs.
  • Fig. S6. Validation of MCC950 as a potent inhibitor of NLRP3 inflammasome activation in microglia.
  • Fig. S7. Additional open-field activity measurements in PFF mice.
  • Fig. S8. Representative images of hyperphosphorylated α-synuclein staining in the substantia nigra of PFF mice.
  • Fig. S9. Representative images and quantitation of hyperphosphorylated α-synuclein staining in the cortex of PFF mice.
  • Fig. S10. Hyperphosphorylated α-synuclein is present within dopaminergic neurons and is associated with ubiquitin in the PFF mouse model.
  • Fig. S11. Total α-synuclein is not altered in PFF mice treated with MCC950.
  • Table S1. Brain and plasma concentrations of MCC950 after 5-day drinking water administration (0.3 mg/ml) to mice.
  • Table S2. Off-target activity of MCC950 and a structural analog from ToxCast/Tox21 datasets.
  • Table S3. Comparison of chemical and pharmacological properties of novel MCC950 analogs.

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Other Supplementary Material for this manuscript includes the following:

  • Table S4. Primary data (Excel file).
  • Movie S1 (.mp4 format). Representative amphetamine-induced rotation videos of 6-OHDA mice with and without MCC950 treatment.
  • Movie S2 (.mp4 format). Representative balance beam videos of PFF mice with and without MCC950 treatment.
  • Movie S3 (.mp4 format). Representative wire-hang videos of PFF mice with and without MCC950 treatment.