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Mechanistic Involvement of the Calpain-Calpastatin System in Alzheimer Neuropathology
https://repo.qst.go.jp/records/47240
https://repo.qst.go.jp/records/47240ec509b7d-5f2f-4f3a-89c4-ffbabd30a5bb
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-08-07 | |||||
| タイトル | ||||||
| タイトル | Mechanistic Involvement of the Calpain-Calpastatin System in Alzheimer Neuropathology | |||||
| 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_6501 | |||||
| 資源タイプ | journal article | |||||
| 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 |
Higuchi, Makoto
× Higuchi, Makoto× Iwata, Nobuhisa× Matsuba, Yukio× Takano, Jiro× Suemoto, Takahiro× Maeda, Jun× Ji, Bin× Ono, Maiko× Staufenbiel, Matthias× Suhara, Tetsuya× Saido, Takaomi× 樋口 真人× 前田 純× 季 斌× 小野 麻衣子× 須原 哲也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The mechanism by which amyloid-β peptide (Aβ) accumulation causes neurodegeneration in Alzheimer's disease (AD) remains unresolved. Given that Aβ perturbs calcium homeostasis in neurons, we investigated the possible involvement of calpain, a calcium-activated neutral protease. We first demonstrated close postsynaptic association of calpain activation with Aβ plaque formation in brains from both patients with AD and transgenic (Tg) mice overexpressing amyloid precursor protein (APP). Using a viral vector-based tracer, we then showed that axonal termini were dynamically misdirected to calpain activation-positive Aβ plaques. Consistently, cerebrospinal fluid from patients with AD contained a higher level of calpain-cleaved spectrin than that of controls. Genetic deficiency of calpastatin (CS), a calpain-specific inhibitor protein, augmented Aβ amyloidosis, tau phosphorylation, microgliosis, and somatodendritic dystrophy, and increased mortality in APP-Tg mice. In contrast, brain-specific CS overexpression had the opposite effect. These findings implicate that calpain activation plays a pivotal role in the Aβ-triggered pathological cascade, highlighting a target for pharmacological intervention in the treatment of AD. | |||||
| 書誌情報 |
The FASEB Journal 巻 26, 号 3, p. 1204-17, 発行日 2012-03 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0892-6638 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 22173972 | |||||
