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Publication
Engineered Neutral Phosphorous Dendrimers Protect Mouse Cortical Neurons and Brain Organoids from Excitotoxic Death
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Advisor(s)
Abstract(s)
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.
Description
Keywords
Phosphorous dendrimers Excitotoxicity Cortical neurons Brain organoids Neuroprotection Mitochondria . Faculdade de Ciências Exatas e da Engenharia
Citation
Romero-Castillo, L.; Ronca, R.-A.; Karpus, A.; Mignani, S.; Majoral, J.-P.; Muñoz-Fernández, M.; Ceña, V. Engineered Neutral Phosphorous Dendrimers Protect Mouse Cortical Neurons and Brain Organoids from Excitotoxic Death. Int. J. Mol. Sci. 2022, 23, 4391. https://doi.org/ 10.3390/ijms23084391
Publisher
MDPI