Abstract：
:Aggregation and intracellular deposition of the protein α-synuclein is an underlying characteristic of Parkinson's disease. α-Synuclein assemblies also undergo cell-cell spreading, facilitating propagation of their cellular pathology. Understanding how cellular interactions and uptake of extracellular α-synuclein assemblies depend on their physical attributes is therefore important. We prepared fragmented fluorescently labeled α-synuclein amyloid fibrils of different average lengths (∼80 nm to >1 μm) and compared their interactions with SH-SY5Y cells. We report that fibrils of all lengths, but not monomers, bind avidly to the cell surface. Their uptake is inversely dependent on their average size, occurs via a heparan sulfate dependent endocytic route, and appears to have a size cutoff of ∼400 nm. The uptake of α-synuclein fibrils, but not monomers, correlates with their cytotoxicity as measured by reduction in metabolic activity, strongly suggesting an intracellular basis for α-synuclein fibril toxicity, likely involving endolysosomes.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Zhang X,Wesén E,Kumar R,Bernson D,Gallud A,Paul A,Wittung-Stafshede P,Esbjörner EKdoi
10.1021/acschemneuro.9b00562subject
Has Abstractpub_date
2020-02-05 00:00:00pages
233-241issue
3issn
1948-7193journal_volume
11pub_type
杂志文章abstract：:Biology has inspired solutions to many engineering problems, including chemical sensing. Modern approaches to chemical sensing have been based on the biological principle of combining cross-selective chemical sensors with a pattern recognition engine to identify odors. Here, we review some recent advances made in mimi...
journal_title：ACS chemical neuroscience
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