The orchestration of subcellular alpha-synuclein pathology in the Parkinson’s disease brain revealed by STED microscopy

摘要: Abstract Post-translational modifications of alpha-synuclein (aSyn), particularly phosphorylation at Serine 129 (Ser129-p) and truncation its C-terminus (CTT), have been implicated in Parkinson’s disease (PD) pathology. To gain more insight the relevance Ser129-p CTT aSyn under physiological pathological conditions, weinvestigated their subcellular distribution patterns normal aged PD brains using highly-selective antibodies combination with 3D multicolor STED microscopy. We show that localizes mitochondria patients controls, whereas organization a cytoplasmic network is strongly associated Nigral Lewy bodies an onion skin-like architecture, structured framework neurofilaments encapsulating core, which displayed high content proteins lipids by label-free CARS The phenotypes antibody-labeled pathology identified this study provide evidence for crucial role body formation.