Fig. 2: Hexosamine-biosynthetic pathway (HBP) is disrupted in synucleinopathy models and DLB patient brain.

A Schematic showing HBP and N-glycosylation pathway. UDP-GlcNAc Uridine-diphosphate-N-acetylglucosamine, F-6-P Fructose-6-phosphate, HK-1 Hexokinase-1, G-6-P glucose-6-phoshate, GFPT2 glutamine: F-6-P transaminase-2, GNA1 GlcN-6P acetyltransferase, acetyl-CoA acetyl coenzyme A, PGM3 GlcNAc phosphomutase, UAP1 UDP-GlcNAc pyrophosphorylase, NAGK N-acetylglucosamine kinase, OST oligosaccharyltransferase, B–F Targeted metabolomic analysis of A53T or Corr iPSn at day 90 by Liquid Chromatography-Mass Spectrometry LC/MS (B) Glucose (n = 4) (C) Glucose-6-Phosphate (Corr n = 3; A53T n = 4) (D) Uridine triphosphate (UTP) (Corr n = 3; A53T n = 4) (E) Glutamine (n = 4) (F) Glutamate (n = 4). G Quantitative RT-PCR analysis of DPAGT1 (n = 6), NS not significant. H Quantitative RT-PCR analysis of GFPT2 mRNA in A53T or Corr iPSn at day 90 (n = 3). I–L Western blot analysis of GFPT2 in (I) SH-SY5Y vector (vec) and stable line overexpressing WT α-syn (Syn) (n = 6), (J) iPSn (Corr and A53T) (n = 6) (K) Non-transgenic control (Con) and A53T transgenic mouse brain (cerebellum) (n = 3) and (L) post-mortem cortical human brain samples from Control (Con) and Dementia with Lewy body patients (DLB). GAPDH was used as loading control. Quantifications are shown on the right (con = 4; DLB n = 5). Scatter plots represent individual culture well replicates, individual mouse brains, or individual human brain samples. For all quantifications, values are the mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Student’s two-sided t-test was used for all comparisons. Source data are provided as a Source Data file.