Modeling alpha-synuclein pathology in a human brain-chip to assess blood-brain barrier disruption
| Autor: | Christopher Y. Le, William Tien-Street, Geraldine A. Hamilton, Iosif Pediaditakis, Lorna Ewart, Elias S. Manolakos, Katia Karalis, Chris Hinojosa, Lee L. Rubin, Konstantia Kodella, Kostas Vekrellis, Dimitris V. Manatakis |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Synucleinopathies
Science General Physics and Astronomy Substantia nigra Biology General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound medicine Humans Gliosis Phosphorylation Neuroinflammation Alpha-synuclein Multidisciplinary Microglia Dopaminergic Neurons Dopaminergic Brain Endothelial Cells Parkinson Disease General Chemistry Human brain Mitochondria nervous system diseases Substantia Nigra medicine.anatomical_structure nervous system chemistry Blood-Brain Barrier Astrocytes alpha-Synuclein medicine.symptom Pericytes Transcriptome Neuroscience |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021) |
| ISSN: | 2041-1723 |
| Popis: | Parkinson’s disease and related synucleinopathies are characterized by the abnormal accumulation of alpha-synuclein aggregates, loss of dopaminergic neurons, and gliosis of the substantia nigra. Although clinical evidence and in vitro studies indicate disruption of the Blood-Brain Barrier in Parkinson’s disease, the mechanisms mediating the endothelial dysfunction is not well understood. Here we leveraged the Organs-on-Chips technology to develop a human Brain-Chip representative of the substantia nigra area of the brain containing dopaminergic neurons, astrocytes, microglia, pericytes, and microvascular brain endothelial cells, cultured under fluid flow. Our αSyn fibril-induced model was capable of reproducing several key aspects of Parkinson’s disease, including accumulation of phosphorylated αSyn (pSer129-αSyn), mitochondrial impairment, neuroinflammation, and compromised barrier function. This model may enable research into the dynamics of cell-cell interactions in human synucleinopathies and serve as a testing platform for target identification and validation of novel therapeutics. |
| Databáze: | OpenAIRE |
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