Figure 5

AT1 accumulates at the nuclear envelope and within nuclei. In dopamine neurons, AT1 is typically localized to the cytoplasm, to the perinuclear structures (arrowheads), and to the nuclei (A). In addition, buildup of the AT1 within nuclei identified by arrowheads in (B) often coincides with irregularly-shaped nuclei with chromatin irregularities identified by the arrows (C). In neurons, as well as in some non-neuronal cells as depicted here, AT1 co-localizes with nucleoporin 62 (p62), a component of the nuclear pore central channel (D-G). Quantification of AT1 immunofluorescence within nuclei of TH+ neurons in neurologically intact individuals/AMC and in prePD and in PD patients (H) shows selective changes in AT1 corresponding to the disease progression. Notably, the abundance of nuclear AT1 in nigrosome 1 remains constant as disease advances whereas, in the matrix, the abundance of nuclear AT1 is gradually reduced as a function of disease progression following the trajectory of the total AT1 decline within the entire neuron (Figure 4I). Scale bars are 10 μm. Asterisks in (A and B) identify neuromelanin and the asterisk in (H) identifies a significant difference between matrix of AMC and PD.