2022年1月10日 · We demonstrated the effects of APP-CTFs-related pathology using induced neural stem cells (iNSCs) from AD patient-derived fibroblasts. APP-CTFs accumulation was demonstrated to mainly occur...

这一刀剪在Aβ序列的N端，APP就分成了APPSβ（也可以写成sAPPβ）和C端的β-CTF，刚才说到的Swe突变就会导致APP的β剪切更容易发生。 这些带“β”家伙的出现往往就意味着Aβ含量的增加，因为β-CTF再被γ剪切酶剪切后“大魔王”Aβ就正式出场了。 图1. APP剪切过程. 这里顺道提一下，γ剪切酶与α和β剪切酶不一样，后面两个刀法精准，剪切位置固定；而γ则对α-CTF或者β-CTF的剪切飘忽不定，所以Aβ指的是一类短肽（36-43个氨基酸都有可能），而不是固定大小的片 …

2017年5月30日 · In this study we investigated if APP-CTFs are detectable in CSF, characterized the major APP-CTF immunoreactive band, and determined whether the levels of this peptide fragment are altered in...

2024年6月17日 · Our findings imply a critical role for balanced APP-CTF levels in LE/Lys-ER membrane contact sites (MCSs) to maintain endolysosomal homeostasis. The detrimental effects of elevated APP-CTFs herein underscore their significance as a therapeutic target to address AD progression at an early stage, preceding the appearance of amyloid plaques.

APP, a type I transmembrane protein, undergoes cleavage primarily by α-secretase on the cytoplasmic membrane, producing soluble α-cleavage N-terminal fragment (sAPPα) and α-cleavage C-terminal fragment (α-CTF). Some APP molecules bypass α-cleavage and undergo endocytosis into endocytic compartments, where they are subsequently cleaved by ...

APP-CTFs 积累被证明主要发生在线粒体结构域内，是线粒体功能障碍的原因和结果。APP-CTFs 积累也导致线粒体自噬失败，这已通过增加 LC3-II 和 p62 以及不一致的 PTEN 诱导激酶 1 (PINK1)/E3 泛素连接酶 (Parkin) 募集到线粒体以及线粒体和溶酶体融合失败来验证。

2020年10月20日 · Several lines of recent evidence indicate that the amyloid precursor protein-derived C-terminal fragments (APP-CTFs) could correspond to an etiological trigger of Alzheimer’s disease (AD) pathology. Altered mitochondrial homeostasis is considered an early event in AD development.

2020年10月23日 · 在这里，我们证明在神经母细胞瘤SH-SY5Y细胞中，表达APP瑞典突变或β-分泌酶衍生的APP-CTF片段（C99）结合β-和γ-分泌酶抑制，APP-CTF的积累独立于Aβ触发过度的线粒体形态改变，其与线粒体活性氧生成增强有关。 APP-CTFs的积累也引起基础的有丝分裂功能衰竭，表现为LC3的转化增强、LC3-I和/或LC3-II的积累、SQSTM1/p62的不降解、线粒体中Parkin和PINK1不一致的募集、膜和基质线粒体蛋白水平的提高以及线粒体与溶酶体融合不足。 我们还 …

2018年1月18日 · Our results reveal a homeostatic response counteracting lysosomal dysfunction via secretion of atypical exosomes eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate...

Several lines of recent evidence indicate that the amyloid precursor protein-derived C-terminal fragments (APP-CTFs) could correspond to an etiological trigger of Alzheimer's disease (AD) pathology. Altered mitochondrial homeostasis is considered an early event in AD development.