Short Aβ peptides attenuate Aβ42 toxicity in vivo.
Short Aβ peptides attenuate Aβ42 toxicity in vivo.
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DOI：
10.1084/jem.20170600
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发表时间：
2018-01-02
期刊：
影响因子：
--
通讯作者：
Golde TE
中科院分区：
文献类型：
--
作者：
Moore BD;Martin J;de Mena L;Sanchez J;Cruz PE;Ceballos-Diaz C;Ladd TB;Ran Y;Levites Y;Kukar TL;Kurian JJ;McKenna R;Koo EH;Borchelt DR;Janus C;Rincon-Limas D;Fernandez-Funez P;Golde TE
数据表明，短淀粉样蛋白β（Aβ）在体内没有毒性，可以阻止与Aβ42积累相关的毒性。
通过γ-分泌酶处理淀粉样蛋白-β（Aβ）前体蛋白（APP）会产生多种Aβ：Aβ40，短Aβ肽（Aβ37-39）和更长的Aβ肽（Aβ42-43）（Aβ37-39）（Aβ37-39）（Aβ37-39）（Aβ42-43）。为了评估这些肽的病理相关性，我们表达了Aβ36-40和果蝇中的Aβ42-43与Aβ42相比，对Aβ42的固有毒性和潜在的调节作用。冰时，在非转基因小鼠中表达足以驱动Aβ42的冰沉积Aβ38和Aβ40没有沉积或引起行为改变。
Data demonstrate that short amyloid-β (Aβ) peptides are not toxic in vivo and can partially block toxicity associated with Aβ42 accumulation. Moore et al. further validate the use of γ-secretase modulators that lower Aβ42 and increase short Aβs as potential Alzheimer’s disease therapeutics. Processing of amyloid-β (Aβ) precursor protein (APP) by γ-secretase produces multiple species of Aβ: Aβ40, short Aβ peptides (Aβ37–39), and longer Aβ peptides (Aβ42–43). γ-Secretase modulators, a class of Alzheimer’s disease therapeutics, reduce production of the pathogenic Aβ42 but increase the relative abundance of short Aβ peptides. To evaluate the pathological relevance of these peptides, we expressed Aβ36–40 and Aβ42–43 in Drosophila melanogaster to evaluate inherent toxicity and potential modulatory effects on Aβ42 toxicity. In contrast to Aβ42, the short Aβ peptides were not toxic and, when coexpressed with Aβ42, were protective in a dose-dependent fashion. In parallel, we explored the effects of recombinant adeno-associated virus–mediated expression of Aβ38 and Aβ40 in mice. When expressed in nontransgenic mice at levels sufficient to drive Aβ42 deposition, Aβ38 and Aβ40 did not deposit or cause behavioral alterations. These studies indicate that treatments that lower Aβ42 by raising the levels of short Aβ peptides could attenuate the toxic effects of Aβ42.
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DOI：
10.1186/s13195-016-0199-5
发表时间：
2016-08-30
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
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发表时间：
2012-06-14
期刊：
Alzheimer's research & therapy
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