Fig. 1: Lysosomal degradation of α-syn.
a Schematic representation of the primary amino acid sequences of 1–140 (top) and 66–140 (bottom), coloring basic (blue) and acidic (red) residues. Charged residues that participate in salt bridges within the shared α-syn fibril core (residues 36–99) are indicated3,4,6,7,11,22,23,37,38,39,40,41,44,45,46,55,56,57,61,79. b Schematic representation of the primary amino acid sequence of α-syn with cleavage sites generated for either soluble (cyan) or fibrillar (black) α-syn. Residues 36–99 (light gray) show cryoEM fibril core while residues 61–95 denote the NAC region (dark gray). c α-Syn peptide fragments derived from lysosomal degradation of soluble (cyan) and fibrillar (black) α-syn. Brain lysosomal extracts were obtained from a 10-month-old male mouse. Fragment masses and residue assignments are reported in Supplementary Table 1. Previously identified fragments from PD patients are denoted by asterisks. Effect of mouse age on specific lysosomal protease activities. Brain lysosomal extracts were obtained from two female mice aged 2 and 17 months. Fluorogenic substrates d Ac-RR-AMC for CtsB, e Ac-FR-AMC for CtsL, f MCA-GKPILEFRKL(Dnp)-D-R-NH2 for CtsD, and g AENK-AMC for AEP were incubated with lysosomal extracts (10–40 µg total protein) at pH 5.0 with 5 mM DTT, 37 °C. Fluorescence was recorded as a function of time (30 and 60 min), and relative fluorescence units (RFU) are reported (n = 3 technical replicates). Data are presented as mean values ± SD. Source data are provided as a Source Data file.
