title: In Vitro Modulation of TrkB Receptor Signaling upon Sequential Delivery of Curcumin-DHA Loaded Carriers Towards Promoting Neuronal Survival.
abstract: To in vitro investigate the capacity of carrier-free and lipid-nanoparticle (NP)-encapsulated phytochemical compounds to prevent neuronal damage through neurotrophin potentiating activities. Delivery of molecules promoting the neurotrophin receptor signaling in the central nervous system (CNS) present ongoing interest for combination therapy development.
  
  
  
  Super-resolution Stimulated Emission Depletion (STED) microscopy imaging and flow cytometry analysis were employed to study the expression of the neurotrophin TrkB receptor in a neuronal cell model, which is highly responsive to binding of brain-derived neurotrophic factor (BDNF). Dual drug-loaded nanoparticle formulations, prepared by self-assembly of lyotropic lipids and PEGylated amphiphile derivatives, were delivered to differentiated human neuroblastoma SH-SY5Y cells subjected to degenerative conditions.
  
  
  
  The expression of BDNF in the intra and extracellular domains was quantified by ELISA and flow cytometry after sequential treatment of the degenerating SH-SY5Y cells by neurotherapeutic formulations. Flow cytometry was also used to assess the phosphorylation of the transcription factor cAMP response element-binding protein (CREB) in the intracellular domain as a result of the treatment by nanoformulations.
  
  
  
  Over time, dual drug formulations (curcumin and docosahexaenoic acid (DHA)) promoted the neuronal survival and repair processes through enhanced BDNF secretion and increased phosphorylation of CREB as compared to untreated degenerating cells.
authors.affiliation: Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, LabEx LERMIT, 5 rue J.-B. Clément, 92296, Châtenay-Malabry cedex, France.
authors.forename: Luis P B
authors.initials: LP
authors.lastname: Guerzoni
authors.affiliation: MIPSIT, Paris-Saclay Institute of Therapeutic Innovation (IPSIT-UMS3679 CNRS, US31 INSERM), Faculty of Pharmacy, Univ Paris Sud, Université Paris-Saclay, 5 rue J.-B. Clément, 92296, Châtenay-Malabry, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Nicolas
authors.affiliation: Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, LabEx LERMIT, 5 rue J.-B. Clément, 92296, Châtenay-Malabry cedex, France. angelina.angelova@u-psud.fr.
authors.forename: Angelina
authors.identifier: 0000-0002-0285-0637
authors.initials: A
authors.lastname: Angelova
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D020813:Receptor, trkB / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004337:Drug Carriers; D008055:Lipids; D004281:Docosahexaenoic Acids; D011092:Polyethylene Glycols; D020813:Receptor, trkB; D003474:Curcumin
keywords: BDNF; CREB transcription factor; DHA; curcumin; multidrug formulations