Maintenance of membrane organization in the aging mouse brain as the determining factor for preventing receptor dysfunction and for improving response to anti-Alzheimer treatments.
2017
Colin, Julie | Thomas, Mélanie | Pauron, Lynn Anne | Pinçon, Anthony | Lanhers, Marie-Claire | Corbier, Catherine | Claudepierre, Thomas | Yen Potin, Frances T. | Oster, Thierry | Malaplate-Armand, Catherine | Unité de Recherches Animal et Fonctionnalités des Produits Animaux (URAFPA) ; Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL) | Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Although a major risk factor for Alzheimer's disease (AD), the "aging" parameter is not systematically considered in preclinical validation of anti-AD drugs. To explore how aging affects neuronal reactivity to anti-AD agents, the ciliary neurotrophic factor (CNTF)-associated pathway was chosen as a model. Comparison of the neuroprotective properties of CNTF in 6- and 18-month old mice revealed that CNTF resistance in the older animals is associated with the exclusion of the CNTF-receptor subunits from rafts and their subsequent dispersion to non-raft cortical membrane domains. This age-dependent membrane remodeling prevented both the formation of active CNTF-receptor complexes and the activation of prosurvival STAT3 and ERK1/2 pathways, demonstrating that age-altered membranes impaired the reactivity of potential therapeutic targets. CNTF-receptor distribution and CNTF signaling responses were improved in older mice receiving dietary docosahexaenoic acid, with CNTF-receptor functionality being similar to those of younger mice, pointing toward dietary intervention as a promising adjuvant strategy to maintain functional neuronal membranes, thus allowing the associated receptors to respond appropriately to anti-AD agents.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
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تم تزويد هذا السجل من قبل Institut national de la recherche agronomique
