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J Parkinsons Dis. 2016 Jun 16;6(3):569-79. doi: 10.3233/JPD-160835.

Reduction of Immunoreactivity Against the C-Terminal Region of the Intracellular α-Synuclein by Exogenous α-Synuclein Aggregates: Possibility of Conformational Changes.

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Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Department of Neurology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan.
Department of Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.



The formation of intracellular aggregates containing α-synuclein (α-syn) is a main pathological feature of Parkinson disease. The propagation of α-syn aggregation via cell-to-cell transmission has been implicated in the progression of Parkinson disease.


Our aim is to clarify the molecular mechanisms underlying the formation of intracellular aggregation by extracellular α-syn.


We investigated the effects of exogenous α-syn aggregates on intracellular α-syn immunoreactivity in α-syn-overexpressing SH-SY5Y cells using two antibodies to distinct epitopes of α-syn. To obtain α-syn aggregates, α-syn solution was aged with continuous agitation.


Immunoreactivity against the acidic C-terminal domain of the intracellular α-syn was reduced by exposure to agedα-syn, whereas that against the hydrophobic non-amyloid component region was not changed. The reduction in immunoreactivity was not suppressed by protease inhibitors but was mimicked by neutralization of the negative charges on the C-terminal of the intracellular α-syn induced by spermine or extracellular acidification.


These results suggest that the reduction in immunoreactivity is attributed not to proteolytic cleavage but to a conformational change at the C-terminus of the intracellular α-syn. The conformational change at the C-terminus of the intracellular α-syn might be involved in an initial step of fibril formation by exogenous α-syn aggregates.


Parkinson disease; conformational change; fibril; proteolysis; α-synuclein

[Indexed for MEDLINE]

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