Modulators of vesicular glutamate transporters : development of pharmacological and diagnostic tools for Alzheimer's disease
type: Dataset
description: Vesicular glutamate transporters (VGLUTs) are involved in the recapture and storage of glutamate from cytol to secretory synaptic vesicules. Since their recent characterization in 2000, their implication in several neurodegenerative disorders have been demonstrated. They play a crucial role in glutamatergic neurotransmission. Natural dyes, such as Rose Bengal and Tryptan Blue are the best known inhibitors with IC50 values of 25 and 50 nM, respectively. Firstly, we designed and optimized a series of analogues based on the synthon Rose Bengal (non-competitive inhibitor). This work has especially enabled to highlight the effect of tautomeric forms (quinone and lactone) on the inhibition of VGLUTs. Thus, the quinone form, present at physiological pH, was confirmed as the only able to block the reuptake of glutamate. Secondly, we have been interested in the family of Trypan Blue (competitive inhibitor) and we determined the minimal active structure in order to render these molecules more "drug-like". Indeed, the interest of this project is to develop small structures easily radiomarquable to use in a physiopathological context.
identifier: NNT: 2012PA05P639
issued: 2026-05-07T16:20:00.324300
language: fr
modified: 2026-05-07T16:20:00.324304
contact point: Organization
  fn: CCSD
keyword: bleu-trypan
keyword: chimothechemical-sciencesother
keyword: colorants
keyword: dyes
keyword: glutamate
keyword: infoeu-reposemanticsdoctoralthesis
keyword: neurotransmission
keyword: rose-bengal
keyword: rose-bengale
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: structure-activite
keyword: structure-activity
keyword: theses
keyword: trypan-blue
keyword: vglut
landing page: https://theses.hal.science/tel-00923157

Modulators of vesicular glutamate transporters : development of pharmacological and diagnostic tools for Alzheimer's disease
type: Distribution
format: HTML
issued: 2026-05-07T16:20:00.333335
modified: 2026-05-07T16:20:00.302803
access URL: https://theses.hal.science/tel-00923157

test_moissonnage_selune
type: Agent