TY - JOUR
TI - Modeling alpha-synuclein pathology in a human brain-chip to assess blood-brain barrier disruption
AU - Pediaditakis, I.
AU - Kodella, K.R.
AU - Manatakis, D.V.
AU - Le, C.Y.
AU - Hinojosa, C.D.
AU - Tien-Street, W.
AU - Manolakos, E.S.
AU - Vekrellis, K.
AU - Hamilton, G.A.
AU - Ewart, L.
AU - Rubin, L.L.
AU - Karalis, K.
JO - Nature Communications
PY - 2021
VL - 12
TODO - 1
SP - null
PB - Institute of Geographic Sciences and Natural Resources Research
SN - 2041-1723
TODO - 10.1038/s41467-021-26066-5
TODO - alpha synuclein;  microtubule associated protein 2;  reactive oxygen metabolite;  trehalose;  alpha synuclein;  transcriptome, blood;  brain;  nervous system disorder;  neurology;  pathology, adult;  Article;  astrocyte;  blood brain barrier;  brain;  cell interaction;  dopaminergic nerve cell;  endothelium cell;  fluid flow;  gene ontology;  human;  human cell;  human tissue;  microglia;  mitochondrion;  nervous system inflammation;  Parkinson disease;  pericyte;  RNA sequencing;  substantia nigra;  synucleinopathy;  transcriptomics;  blood brain barrier;  diagnostic imaging;  gliosis;  metabolism;  pathology;  phosphorylation;  substantia nigra, alpha-Synuclein;  Astrocytes;  Blood-Brain Barrier;  Brain;  Dopaminergic Neurons;  Endothelial Cells;  Gliosis;  Humans;  Microglia;  Mitochondria;  Parkinson Disease;  Pericytes;  Phosphorylation;  Substantia Nigra;  Synucleinopathies;  Transcriptome
TODO - 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. © 2021, The Author(s).
ER -