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Selective autophagy in neurons and its involvement in the tau pathogenesis
https://repo.qst.go.jp/records/70537
https://repo.qst.go.jp/records/705372962d705-f0f0-4a75-be7b-d141e10809fd
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-09-17 | |||||
| タイトル | ||||||
| タイトル | Selective autophagy in neurons and its involvement in the tau pathogenesis | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Ono, Maiko
× Ono, Maiko× Ki, Hin× Maruyama, Masahiro× Maeda, Jun× Minamihisamatsu, Takeharu× Suhara, Tetsuya× Higuchi, Makoto× 小野 麻衣子× 季 斌× 丸山 将浩× 前田 純× 南久松 丈晴× 須原 哲也× 樋口 真人 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | In Alzheimer's disease, hyperphosphorylated tau proteins assemble into fibri ls, making up neurofibrillary tangles (NFTs), and are involved in neuronal l oss. It is hypothesized that packaging of abnormal tau into NFTs protects ne urons against tau-induced neurodegeneration, while molecular mediators of NF T formation versus accumulation of neurotoxic, low-order tau assemblies rema in unidentified. p62 promotes autophagic degradation of ubiquitinated protei ns, and sequesters them by forming an inclusion body. In mice transgenic for mutant human P301S tau protein, NFTs are abundantly developed in the spinal cord and brainstem but are accompanied by only modest neuronal loss in thes e areas. By contrast, massive neuron death without deposition of NFTs occurs in the hippocampus. Here, we investigated regional differences in levels of p62 and their association with tau lesions between the brainstem and hippoc ampus of P301S and wild-type mice to analyze roles of p62 in the tau pathoge nesis. Immunoreactivity for p62 was found in brainstem neurons of wild-type mice, and this immunolabeling was markedly intensified with accumulation of phosphorylated and ubiquitinated tau in P301S mice, indicating recruitment o f p62 to packaging of hyperphosphorylated and ubiquitinated tau. Meanwhile, p62 was barely detectable in somas of hippocampal pyramidal neurons in both wild-type and P301S mice. In these hippocampal neurons, diffuse signals of p hosphorylated tau spatially overlapped with ubiquitin but not p62 immunoreac tivity. Moreover, autophagic activities in the hippocampus were higher than that in the brainstem as assessed by immunoblotting for LC3. These findings suggest that p62 and other components of autophagy are constitutively consum ed at high levels in hippocampal neurons of P301S mice, leading to insuffici ent reserve capacity for autophagic clearance of hyperphosphorylated tau and its segregation into inclusions and eventually neurotoxicity by misfolded b ut unpackaged tau. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 第34回日本神経科学大会（Neuro2011） | |||||
| 発表年月日 | ||||||
| 日付 | 2011-09-17 | |||||
| 日付タイプ | Issued | |||||
