Engineered Neutral Phosphorous Dendrimers Protect Mouse Cortical Neurons and Brain Organoids from Excitotoxic Death

Autor: Inmaculada Posadas, Laura Romero-Castillo, Rosa-Anna Ronca, Andrii Karpus, Serge Mignani, Jean-Pierre Majoral, Mariángeles Muñoz-Fernández, Valentín Ceña
Přispěvatelé: Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Est (UPE), Centro de Química da Madeira, Universidade da Madeira (UMA), Hospital General Universitario 'Gregorio Marañón' [Madrid], European Union NextGenerationEU (PRTR-C17.I1), Spanish Ministerio de Ciencia e Innnovación (project PID2020-120134RBI00 from MINECO/AEI/FEDER/UE), Instituto de Salud Carlos III (ISCIII, projects RETIC PT17/0015/0042, PI19/01638), Junta de Comunidades de Castilla-La Mancha (project SBPLY/19/180501/000067), ERANET Euronanomed Program (project NANO4GLIO), Action Nano2Clinic (CA17140) / COST, CNRS, FCT-Fundação para a Ciência e a Tecnologia (Base Fund UIDB/00674/2020 and Programmatic Fund UIDP/00674/2020, Portuguese Government Funds), ARDITI-Agência Regional para o Desenvolvimento da Investigação Tecnologia e Inovação through the project M1420-01-0145-FEDER-000005-CQM+ (Madeira 14-20 Program)
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences; Volume 23; Issue 8; Pages: 4391
International Journal of Molecular Sciences
International Journal of Molecular Sciences, 2022, 23 (8), pp.4391. ⟨10.3390/ijms23084391⟩
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms23084391⟩
Popis: International audience; Nanoparticles are playing an increasing role in biomedical applications. Excitotoxicity plays a significant role in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s or Parkinson’s disease. Glutamate ionotropic receptors, mainly those activated by N-methyl-D-aspartate (NMDA), play a key role in excitotoxic death by increasing intraneuronal calcium levels; triggering mitochondrial potential collapse; increasing free radicals; activating caspases 3, 9, and 12; and inducing endoplasmic reticulum stress. Neutral phosphorous dendrimers, acting intracellularly, have neuroprotective actions by interfering with NMDA-mediated excitotoxic mechanisms in rat cortical neurons. In addition, phosphorous dendrimers can access neurons inside human brain organoids, complex tridimensional structures that replicate a significant number of properties of the human brain, to interfere with NMDA-induced mechanisms of neuronal death. Phosphorous dendrimers are one of the few nanoparticles able to gain access to the inside of neurons, both in primary cultures and in brain organoids, and to exert pharmacological actions by themselves.
Databáze: OpenAIRE
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