2020年
脂肪酸結合タンパク質FABP3による新たなαシヌクレインの細胞内取込み制御と神経変性機構
日本薬理学会年会要旨集
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- 巻
- 93
- 号
- 0
- 開始ページ
- 2
- 終了ページ
- O-065
- 記述言語
- 日本語
- 掲載種別
- DOI
- 10.1254/jpssuppl.93.0_2-O-065
- 出版者・発行元
- 公益社団法人 日本薬理学会
<p>α-Synuclein is an abundant neuronal protein that accumulates in insoluble inclusions in Parkinson's disease and other synucleinopathies. Fatty acids partially regulate α-Synuclein accumulation, and mesencephalic dopaminergic neurons highly express fatty acid-binding protein 3 (FABP3). We previously demonstrated that FABP3 knockout mice show decreased α-Synuclein oligomerization and neuronal degeneration of tyrosine hydroxylase (TH)-positive neurons in vivo. In this study, we newly investigated the importance of FABP3 in α-Synuclein uptake, 1-methyl-4-phenylpyridinium (MPP+)-induced axodendritic retraction, and mitochondrial dysfunction. To disclose the issues, we employed cultured mesencephalic neurons derived from wild type or FABP3-/- C57BL6 mice and performed immunocytochemical analysis. We demonstrated that TH+ neurons from FABP3+/+ mice take up α-Synuclein monomers while FABP3-/- TH+ neurons do not. The formation of filamentous α-Synuclein inclusions following treatment with MPP+ was observed only in FABP3+/+, and not in FABP3-/- neurons. Notably, detailed morphological analysis revealed that FABP-/- neurons did not exhibit MPP+-induced axodendritic retraction. Moreover, FABP3 was also critical for MPP+-induced reduction of mitochondrial activity and the production of reactive oxygen species. These data indicate that FABP3 is critical for α-Synuclein uptake and mitochondrial functions in dopaminergic neurons, thereby preventing synucleinopathies, including Parkinson's disease.</p>
- リンク情報
- ID情報
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- DOI : 10.1254/jpssuppl.93.0_2-O-065
- CiNii Articles ID : 130007811569