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Cell Tissue Res. 2018 Jul;373(1):175-182. doi: 10.1007/s00441-017-2775-9. Epub 2018 Feb 6.

Release and uptake of pathologic alpha-synuclein.

Author information

1
Neurology, Ulm University, Ulm, Germany.
2
Neurology, Ulm University, Ulm, Germany. karin.danzer@uni-ulm.de.

Abstract

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease, which is characterized by severe loss of dopaminergic neurons and formation of Lewy bodies, which are rich in aggregated alpha-synuclein (α-syn). Two decades of intensive research have compiled a massive body of evidence that aggregation of α-syn is a critical process in PD and other synucleinopathies. The dissemination of Lewy body pathology throughout the central nervous system strongly suggests a cell-to-cell transmission of α-syn. Although in vitro and in vivo evidence has convincingly demonstrated that aggregation-prone α-syn can spread from cell to cell, the exact mechanisms and the role for the disease pathology remain elusive. Except for cases of direct contact, the transmission of α-syn from cell to cell requires that α-syn is released to the extracellular space and taken up by recipient cells. Furthermore, internalized α-syn needs to gain access to the cytoplasm and/or target organelles of the recipient cell. Here, we review the current state of knowledge about release and uptake of α-syn and discuss the key questions that remain unanswered.

KEYWORDS:

Alpha synuclein; Cell-to-cell transmission; Exosomes; Parkinson’s disease; Spreading

PMID:
29411106
DOI:
10.1007/s00441-017-2775-9
[Indexed for MEDLINE]

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