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

International Journal of Molecular Sciences

Serge Mignani¹  Mariángeles Muñoz-Fernández²  Andrii Karpus³  Jean-Pierre Majoral³  Laura Romero-Castillo⁴  Valentín Ceña⁴  Inmaculada Posadas⁴  Rosa-Anna Ronca⁴ 

[1] Department Medicinal Chemistry, Université Paris Descartes, 75006 Paris, France;Department of Immunology, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain;Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique (CNRS), 31400 Toulouse, France;Unidad Asociada Neurodeath, Facultad de Medicina, Universidad de Castilla-La Mancha, 02006 Albacete, Spain;

关键词: phosphorous dendrimers;    excitotoxicity;    cortical neurons;    brain organoids;    neuroprotection;    mitochondria;   

DOI  :  10.3390/ijms23084391

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown