Comparing the Effects of Taurine and 3-Sulfopropanoic Acid, a Metabolite of Tramiprosate, on ApoE4 Pathological Aggregation: Implications for Alzheimer's Disease
Apolipoprotein E4 (ApoE4) is a major genetic risk factor for Alzheimer's disease. Its pathological aggregation can be mitigated by tramiprosate and its metabolite 3-sulfopropanoic acid, along with their impact on the transcription of genes, expression of proteins, and production of lipids. Taurine (TRN) is a close chemical analogue of tramiprosate (TMP) with an extra carbon atom , demonstrating protective effects against aging. Using an integrated approach involving static light scattering, hydrogen-deuterium exchange mass spectrometry, molecular dynamics, and studies of cerebral organoids, we evaluated the effects of 3-sulfopropanoic acid and taurine on ApoE4 aggregation, as well as their impact on organoid transcriptomics and proteomics. Our results reveal that taurine effectively inhibits ApoE4 aggregation, comparable to 3-sulfopropanoic acid, and ameliorates the pathophysiological phenotype of ApoE4 in cerebral organoids, aligning it more closely with the ApoE3 phenotype. These findings suggest that taurine may have potential as a therapeutic agent against Alzheimer's disease, particularly in ApoE4/E4 carriers. Overall design: Comparative gene expression analysis of three biological replicates of cerebral organoids (Vanova et al., 2023; each condition sample consisted of several organoids ~10) treated with tramiprosate/taurine/untreated at D50 of cell culture to D100.