RRC ID 62044
Author Konno M, Hasegawa T, Baba T, Miura E, Sugeno N, Kikuchi A, Fiesel FC, Sasaki T, Aoki M, Itoyama Y, Takeda A.
Title Suppression of dynamin GTPase decreases α-synuclein uptake by neuronal and oligodendroglial cells: a potent therapeutic target for synucleinopathy.
Journal Mol Neurodegener
Abstract BACKGROUND:The intracellular deposition of misfolded proteins is a common neuropathological hallmark of most neurodegenerative disorders. Increasing evidence suggests that these pathogenic proteins may spread to neighboring cells and induce the propagation of neurodegeneration.
RESULTS:In this study, we have demonstrated that α-synuclein (αSYN), a major constituent of intracellular inclusions in synucleinopathies, was taken up by neuronal and oligodendroglial cells in both a time- and concentration-dependent manner. Once incorporated, the extracellular αSYN was immediately assembled into high-molecular-weight oligomers and subsequently formed cytoplasmic inclusion bodies. Furthermore, αSYN uptake by neurons and cells of the oligodendroglial lineage was markedly decreased by the genetic suppression and pharmacological inhibition of the dynamin GTPases, suggesting the involvement of the endocytic pathway in this process.
CONCLUSIONS:Our findings shed light on the mode of αSYN uptake by neuronal and oligodendroglial cells and identify therapeutic strategies aimed at reducing the propagation of protein misfolding.
Volume 7
Pages 38
Published 2012-8-14
DOI 10.1186/1750-1326-7-38
PMID 22892036
PMC PMC3479026
MeSH Animals Blotting, Western Cell Line Coculture Techniques Dynamins / antagonists & inhibitors* Endocytosis Enzyme Inhibitors Fluorescent Antibody Technique Humans Inclusion Bodies / metabolism Inclusion Bodies / pathology Mice Microscopy, Confocal Neurodegenerative Diseases / metabolism* Neurodegenerative Diseases / pathology Neurons / metabolism* Neurons / pathology Oligodendroglia / metabolism* Oligodendroglia / pathology alpha-Synuclein / metabolism*
IF 9.599
Human and Animal Cells KG-1-C(RCB0270)