Fig. 6: Changes in MQC proteins in PD neurons with α-Synuclein aggregation.
From: Parkinson’s disease neurons exhibit alterations in mitochondrial quality control proteins
a Example IMC images of anti-phosphorylated α-Synuclein Ser129(α-Syn) antibody labelling in a TH-positive neuron, showing Lewy body within the neuronal soma and Lewy neurites. Scale bar, 20 µm. b To investigate the response of tested signalling proteins to α-Syn pathology, intra-individual analysis of changes in the protein abundance was performed between PD neurons with and without α-Syn aggregates (signal pixel intensity>5, the number of adjacent positive pixel > 3), using Bayesian Estimation modelling (µ1, α-Syn positive; µ2, α-Syn negative). Each dot represents an individual case (Number of neurons analysed, PD03, 04 &07, n = 44, 39 &11); bars and lines represent the mean and SD; dot size shows the effect size. c Corresponding to the response analysis, three TH-positive neurons selected from PD03 (male, 80 yrs) with varying degree of α-Syn aggregation were demonstrated, alongside signals from the three signalling proteins, phosphorylated ubiquitinSer65 (pUb), LonP and HTRA2 which showed the highest level of increases in α-Syn positive neurons, compared to the α-Syn negative ones among tested proteins. Scale bar, 20 µm. d Proportion of neurons with α-Synuclein or/and pUb aggregates were calculated to support the observation of their co-existence within the PD neurons. Each dot represents an individual case; boxplots show median and mean (triangle) 25th and 75th percentile, with whiskers indicating 95th upper/lower interquartile range. e–g LMM analysis further confirmed the changes of pUb, LonP and HTRA2 to α-Syn pathology at a group level (6/8 PD cases, n = 121 neurons analysed; p < 0.05).
