Aggregate-prone brain regions in Parkinson's disease are rich in unique N-terminus α-synuclein conformers with high proteolysis susceptibility.

ABSTRACT: In Parkinson's disease (PD), and other α-synucleinopathies, α-synuclein (α-Syn) aggregates form a myriad of conformational and truncational variants. Most antibodies used to detect and quantify α-Syn in the human brain target epitopes within the C-terminus (residues 96-140) of the 140 amino acid protein and may fail to capture the diversity of α-Syn variants present in PD. We sought to investigate the heterogeneity of α-Syn conformations and aggregation states in the PD human brain by labelling with multiple antibodies that detect epitopes along the entire length of α-Syn. We used multiplex immunohistochemistry to simultaneously immunolabel tissue sections with antibodies mapping the three structural domains of α-Syn. Discrete epitope-specific immunoreactivities were visualised and quantif

SUBMITTER: Wiseman JA 

PROVIDER: S-EPMC10762179 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature