english
français
RP2E INRA Université de Lorraine

Publications

Improved neuroprotection provided by drug combination in neurons exposed to cell-derived soluble amyloid-beta peptide.

Journal of Alzheimer's Disease, 52 (3), pp. 975-987.

Colin, J., Allouche, A., Chauveau, F., Corbier, C., Gregory-Pauron, L., Lanhers, M.-C., Claudepierre, T., Yen, F.T., Oster, T., Malaplate-Armand, C.

2016

Oligomeric amyloid-ß (Aβ) peptide contributes to impaired synaptic connections and neurodegenerative processes, and as such, represents a primary therapeutic target for Alzheimer's disease (AD)-modifying approaches. However, the lack of efficacy of drugs that inhibit production of Aß demonstrates the need for a better characterization of its toxic effects, both on synaptic and neuronal function. Here, we used conditioned medium obtained from recombinant HEK-AßPP cells expressing the human amyloid-β protein precursor (Aß-CM), to investigate Aß-induced neurotoxic and synaptotoxic effects. Characterization of Aß-CM revealed that it contained picomolar amounts of cell-secreted Aß in its soluble form. Incubation of primary cortical neurons with Aß-CM led to significant decreases in synaptic protein levels as compared to controls. This effect was no longer observed in neurons incubated with conditioned medium obtained from HEK-AßPP cells grown in presence of the γ-secretase inhibitor, Semagacestat or LY450139 (LY-CM). However, neurotoxic and pro-apoptotic effects of Aß-CM were only partially prevented using LY-CM, which could be explained by other deleterious compounds related to chronic oxidative stress that were released by HEK-AßPP cells. Indeed, full neuroprotection was observed in cells exposed to LY-CM by additional treatment with the antioxidant resveratrol, or with the pluripotent n-3 polyunsaturated fatty acid docosahexaenoic acid. Inhibition of Aß production appeared necessary but insufficient to prevent neurodegenerative effects associated with AD due to other neurotoxic compounds that could exert additional deleterious effects on neuronal function and survival. Therefore, association of various types of protective agents needs to be considered when developing strategies for AD treatment.

Imprimer le document

Voir le document sur le site de l'éditeur

167 Publications depuis 2019

Imprimer le listing

2024

ACL - Articles comité de lecture référencés bases de données HCÉRES

2023

ACL - Articles comité de lecture référencés bases de données HCÉRES

2022

ACL - Articles comité de lecture référencés bases de données HCÉRES

2021

ACL - Articles comité de lecture référencés bases de données HCÉRES

2020

ACL - Articles comité de lecture référencés bases de données HCÉRES

2019

ACL - Articles comité de lecture référencés bases de données HCÉRES

Voir les productions antérieures

Toutes les productions scientifiques