Fig. 1. Extensive inflammasome activation and microglial NLRP3 expression is observed in PD patient brains and animal models.
(A) Western blot and (B) densitometric analysis for caspase-1 and ASC from substantia nigra tissue lysates obtained from PD patients and control subjects (n=5–6/group). (C, D) Immunohistochemistry of key inflammasome components NLRP3 (green in C) and ASC (red in D), and Iba-1-positive microglia in substantia nigra tissue sections of postmortem PD patients and age-matched controls. Magnification x40, scale bar 20μm. (E, F) Immunohistochemistry within the striatum of mice 3 days after 6-OHDA or PBS injection, showing NLRP3 (green in E) and ASC (red in F) localized to hypertrophic activated Iba-1-positive microglia in 6-OHDA mice. Magnification x40, scale bar 20μm. (G) Western blot and (H) densitometric analysis for cleaved caspase-1 and ASC in ipsilateral striatal tissue of 6-OHDA and PBS-injected mice at 3 days after injection (n=4 mice/group). (I) Western blot and (J) densitometric analysis for cleaved caspase-1 and ASC in substantia nigra tissue from MitoPark mice (MP) and littermate controls (Ctrl) at 12 and 24 weeks of age (n=2–4 mice/group). (K) Western blot and (L) densitometric analysis for cleaved caspase-1 and ASC in ipsilateral striatal tissue from PBS- and α-synuclein PFF-injected mice at 30 days after injection (n=9 mice/group). Data shown as means ± SEM. *P < 0.05, **P < 0.01 and ***P < 0.001 by Student’s (panels H and J) or Mann-Whitney (panels B and L) t-tests.