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01-08-2010 | Original Paper

Proteinase K-resistant α-synuclein is deposited in presynapses in human Lewy body disease and A53T α-synuclein transgenic mice

Authors: Kunikazu Tanji, Fumiaki Mori, Junsei Mimura, Ken Itoh, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi

Published in: Acta Neuropathologica | Issue 2/2010

Abstract

Abnormally modified α-synuclein is a pathological hallmark of Parkinson’s disease and the other α-synucleinopathies. Since proteinase K (PK) treatment is known to enhance the immunoreactivity of abnormal α-synuclein, we immunohistochemically examined the brain of transgenic (Tg) mice expressing human mutant A53T α-synuclein using this retrieval method. PK treatment abolished the immunoreactivity of α-synuclein in abnormal inclusions as well as of endogenous α-synuclein in Tg mice, whereas PK-resistant α-synuclein was found in the presynaptic nerve terminals, especially in the hippocampus and temporal cortex. In human Lewy body disease, PK-resistant α-synuclein was deposited in Lewy bodies and Lewy neurites, as well as in the presynapses in distinct brain regions, including the hippocampus, temporal cortex and substantia nigra. Biochemical analysis revealed that PK-resistant α-synuclein was detected in the presynaptic fraction in Tg mice and human Lewy body disease. Although PK-resistant α-synuclein was found in the presynapse in Tg mice even at 1 week of age, it was not phosphorylated until at least 8 months of age. Moreover, PK-resistant α-synuclein in the presynapse was not phosphorylated in human Lewy body disease. These findings suggest that phosphorylation is not necessary to cause the conversion of soluble form to PK-resistant α-synuclein. Considering that native α-synuclein is a soluble protein localized to the presynaptic terminals, our findings suggest that PK-resistant α-synuclein may disturb the neurotransmission in α-synucleinopathies.

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Title: Proteinase K-resistant α-synuclein is deposited in presynapses in human Lewy body disease and A53T α-synuclein transgenic mice
Authors: Kunikazu Tanji
Fumiaki Mori
Junsei Mimura
Ken Itoh
Akiyoshi Kakita
Hitoshi Takahashi
Koichi Wakabayashi
Publication date: 01-08-2010
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 2/2010
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-010-0676-z

At a glance: The STEP trials

Springer Medicine

Proteinase K-resistant α-synuclein is deposited in presynapses in human Lewy body disease and A53T α-synuclein transgenic mice

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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