Figure 4.

Lewy-like intraneuronal inclusions in 26S proteasome-depleted neurons. A–D, Representative Lewy-like inclusions in mouse cortical neurons at 6 weeks of age stained with H&E and ubiquitin, α-synuclein, and p62 antibodies, directly compared with Lewy bodies from the brains of patients with dementia with Lewy bodies (100×). No inclusions were observed in the control mouse brains (data not shown). E–I, Ultrastructure of mouse Lewy-like inclusions by EM. The paranuclear inclusion (E; inset; n, nucleus; i, inclusion) contains mitochondria (F, G, arrows), a background matrix of fine filaments (G, arrowheads) and granular material, with peripheral membrane-bound vesicles (F, arrowheads), including double-membraned autophagosome-like dense bodies (H). I, Filamentous α-synuclein is associated with 10 nm gold particles by immunoelectron microscopy. The arrowheads point to particles aligned along distinct filaments. Scale bars: E, 5000 nm; E, 1000 nm; G, H, 500 nm.