Reference : Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and impr...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Social & behavioral sciences, psychology : Neurosciences & behavior
Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer's disease.
[en] La sécrétion par des vecteurs cellulaires de facteur neurotrophique ciliaire prévient les déficits synaptiques et améliore la mémoire dans des souris modèles de la Maladie d'Alzheimer
Garcia, Pierre mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Journal of Neuroscience
Society for Neuroscience
Yes (verified by ORBilu)
[en] Alzheimer's disease ; Ciliary Neurotrophic Factor CNTF ; mouse model
[en] The development of novel therapeutic strategies for Alzheimer’s disease (AD) represents one of the biggest unmet medical needs today. Application of neurotrophic factors able to modulate neuronal survival and synaptic connectivity is a promising therapeutic approach for AD. We aimed to determine whether the loco-regional delivery of ciliary neurotrophic factor (CNTF) could prevent amyloid-beta oligomer-induced synaptic damages and associated cognitive impairments that typify AD. To ensure long-term administration of CNTF in the brain, we used recombinant cells secreting CNTF encapsulated in alginate polymers. The implantation of these bioreactors in the brain of Abeta ligomer-infused mice led to a continuous secretion of recombinant CNTF and was associated with the robust improvement of cognitive performances.Most importantly,CNTF led to full recovery of cognitive function associated with the stabilization of synaptic protein levels in the Tg2576 AD mouse model. In vitro as well as in vivo, CNTF activated a Janus kinase/signal transducer and activator of transcription-mediated survival pathway that prevented synaptic and neuronal degeneration. These preclinical studies suggest that CNTF and/or CNTF receptor-associated pathways may have AD-modifying activity through protection against progressive ABeta-related memory deficits. Our data also encourage additional exploration of ex vivo gene transfer for the prevention and/or treatment of AD.
This work was supported by the Fonds National de la Recherche of Luxembourg, the Re´gion Lorraine, the Ligue Europe´enne Contre la Maladie d’Alzheimer (France), the Fondation pour la Recherche sur le Cerveau (France), the Alzheimer Moselle Nord Association (France), the Alzheimer 54 Association (France), and the France Alzheimer Meurthe et Moselle (France)

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