Dataset Information

Comparing the Effects of Taurine and 3-Sulfopropanoic Acid, a Metabolite of Tramiprosate, on ApoE4 Pathological Aggregation: Implications for Alzheimer's Disease

ABSTRACT: 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 is a close chemical analogue of tramiprosate 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.

ORGANISM(S): Homo Sapiens

SUBMITTER: Marketa Nezvedova

PROVIDER: PXD059743 | panorama | Thu Jul 02 00:00:00 GMT+01:00 2026

REPOSITORIES: PanoramaPublic

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Project description:Proctor2013 - Effect of Aβ immunisation in Alzheimer's disease (deterministic version) Extension of a previously published stochastic model (designed to examine some of the key pathways involved in the aggregation of amyloid-beta (Aβ) and the micro-tubular binding protein tau ( BIOMD0000000286, BIOMD0000000462)) to include the main processes involved in passive and active immunisation against Aβ and then to demonstrate the effects of this intervention on soluble Aβ. This is the deterministic version of the model, the stochastic version is BIOMD0000000634. This model is described in the article: Investigating interventions in Alzheimer's disease with computer simulation models. Proctor CJ, Boche D, Gray DA, Nicoll JA. PLoS ONE 2013; 8(9): e73631 Abstract: Progress in the development of therapeutic interventions to treat or slow the progression of Alzheimer's disease has been hampered by lack of efficacy and unforeseen side effects in human clinical trials. This setback highlights the need for new approaches for pre-clinical testing of possible interventions. Systems modelling is becoming increasingly recognised as a valuable tool for investigating molecular and cellular mechanisms involved in ageing and age-related diseases. However, there is still a lack of awareness of modelling approaches in many areas of biomedical research. We previously developed a stochastic computer model to examine some of the key pathways involved in the aggregation of amyloid-beta (Aβ) and the micro-tubular binding protein tau. Here we show how we extended this model to include the main processes involved in passive and active immunisation against Aβ and then demonstrate the effects of this intervention on soluble Aβ, plaques, phosphorylated tau and tangles. The model predicts that immunisation leads to clearance of plaques but only results in small reductions in levels of soluble Aβ, phosphorylated tau and tangles. The behaviour of this model is supported by neuropathological observations in Alzheimer patients immunised against Aβ. Since, soluble Aβ, phosphorylated tau and tangles more closely correlate with cognitive decline than plaques, our model suggests that immunotherapy against Aβ may not be effective unless it is performed very early in the disease process or combined with other therapies. This model is hosted on BioModels Database and identified by: BIOMD0000000488. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Proctor2013 - Effect of Aβ immunisation in Alzheimer's disease (stochastic version) Extension of a previously published stochastic model (designed to examine some of the key pathways involved in the aggregation of amyloid-beta (A β) and the micro-tubular binding protein tau ( BIOMD0000000286, BIOMD0000000462)) to include the main processes involved in passive and active immunisation against A β and then to demonstrate the effects of this intervention on soluble A β. This is the stochastic version of the model, the deterministic version is BIOMD0000000488. This model is described in the article: Investigating interventions in Alzheimer's disease with computer simulation models. Proctor CJ, Boche D, Gray DA, Nicoll JA. PLoS ONE 2013; 8(9): e73631 Abstract: Progress in the development of therapeutic interventions to treat or slow the progression of Alzheimer's disease has been hampered by lack of efficacy and unforeseen side effects in human clinical trials. This setback highlights the need for new approaches for pre-clinical testing of possible interventions. Systems modelling is becoming increasingly recognised as a valuable tool for investigating molecular and cellular mechanisms involved in ageing and age-related diseases. However, there is still a lack of awareness of modelling approaches in many areas of biomedical research. We previously developed a stochastic computer model to examine some of the key pathways involved in the aggregation of amyloid-beta (Aβ) and the micro-tubular binding protein tau. Here we show how we extended this model to include the main processes involved in passive and active immunisation against Aβ and then demonstrate the effects of this intervention on soluble Aβ, plaques, phosphorylated tau and tangles. The model predicts that immunisation leads to clearance of plaques but only results in small reductions in levels of soluble Aβ, phosphorylated tau and tangles. The behaviour of this model is supported by neuropathological observations in Alzheimer patients immunised against Aβ. Since, soluble Aβ, phosphorylated tau and tangles more closely correlate with cognitive decline than plaques, our model suggests that immunotherapy against Aβ may not be effective unless it is performed very early in the disease process or combined with other therapies. This model is hosted on BioModels Database and identified by: BIOMD0000000634. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Comparing the Effects of Taurine and 3-Sulfopropanoic Acid, a Metabolite of Tramiprosate, on ApoE4 Pathological Aggregation: Implications for Alzheimer's Disease

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