Ubiquitination of a New Form of alpha -Synuclein by Parkin from Human Brain: Implications for Parkinson's Disease

Science ◽  
2001 ◽  
Vol 293 (5528) ◽  
pp. 263-269 ◽  
Author(s):  
H. Shimura
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Brain ◽  
Alpha Synuclein ◽  
New Form

scholarly journals Endogenous α-SYN protein analysis from human brain tissues using single-molecule pull-down assay

2017 ◽  
Author(s):  
Goun Je ◽  
Benjamin Croop ◽  
Sambuddha Basu ◽  
Jialei Tang ◽  
Kyu Young Han ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Brain ◽  
Single Molecule ◽  
Alpha Synuclein ◽  
Postmortem Brains ◽  
Diagnostic Applications ◽  
Reliable Methods ◽  
Molecular Nature

AbstractAlpha-synuclein (α-SYN) is a central molecule in Parkinson’s disease pathogenesis. Despite several studies, the molecular nature of endogenous α-SYN especially in human brain samples is still not well understood due to the lack of reliable methods and the limited amount of bio-specimens. Here, we introduce α-SYN single-molecule pull-down (α-SYN SiMPull) assay combined with in vivo protein crosslinking to count individual α-SYN protein and assess its native oligomerization states from biological samples including human postmortem brains. This powerful single-molecule assay can be highly useful in diagnostic applications using various specimens for neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease.

scholarly journals Modeling alpha-synuclein pathology in a human brain-chip to assess blood-brain barrier disruption

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Iosif Pediaditakis ◽  
Konstantia R. Kodella ◽  
Dimitris V. Manatakis ◽  
Christopher Y. Le ◽  
Chris D. Hinojosa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Human Brain ◽  
Blood Brain Barrier ◽  
Dopaminergic Neurons ◽  
Alpha Synuclein ◽  
Brain Barrier ◽  
Blood Brain

AbstractParkinson’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.

scholarly journals Modeling Alpha-Synuclein Pathology in a Human Brain-Chip to Assess Blood-Brain Barrier Disruption in Parkinson’s Disease

2020 ◽  
Author(s):  
Iosif Pediaditakis ◽  
Konstantia R. Kodella ◽  
Dimitris V. Manatakis ◽  
Chris D. Hinojosa ◽  
Elias S. Manolakos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Human Brain ◽  
Blood Brain Barrier ◽  
Dopaminergic Neurons ◽  
Alpha Synuclein ◽  
Therapeutic Interventions ◽  
Brain Barrier ◽  
Blood Brain

AbstractParkinson’s disease and related synucleinopathies are characterized by the abnormal accumulation of alpha-synuclein aggregates, loss of dopaminergic neurons, and gliosis in 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 remain elusive. Lack of relevant models able to recapitulate the order of events driving the development of the disease in humans has been a significant bottleneck in the identification of specific successful druggable targets. Here we leveraged the Organs-on-Chips technology to engineer 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 is poised to enable research into the dynamics of cell-cell interactions in human synucleinopathies and to serve as testing platform for novel therapeutic interventions, including target identification and target validation.

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