Alzheimer's Disease: A Molecular View of β-Amyloid Induced Morbific Events.
Alzheimer's Disease: A Molecular View of β-Amyloid Induced Morbific Events.
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阿尔茨海默病：β-淀粉样蛋白诱导的发病事件的分子观点。
DOI：
10.3390/biomedicines9091126
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发表时间：
2021-09-01
期刊：
影响因子：
4.7
通讯作者：
Padmanabhan P
中科院分区：
文献类型：
--
作者：
Mohamed Asik R;Suganthy N;Aarifa MA;Kumar A;Szigeti K;Mathe D;Gulyás B;Archunan G;Padmanabhan P
β淀粉样蛋白（Aβ）是阿尔茨海默病（Alzheimer 'sdisease，AD）的一种动力肽，可加速AD的进展。在细胞膜和细胞隔室中，淀粉样前体蛋白（APP）通过β-和γ-分泌酶进行淀粉样裂解并产生Aβ。此外，外部产生的Aβ通过受体介导的内化进入细胞内。Aβ的量升高产生自发聚集，导致细胞器损伤。Aβ通过几种激酶的加速作用刺激tau蛋白的过度磷酸化。Aβ进入线粒体并与其功能复合物相互作用，损害线粒体功能，导致凋亡信号级联反应的激活。Aβ破坏内质网（ER）和高尔基复合体（GC）的Ca 2+和蛋白质稳态，促进细胞器应激并抑制其应激恢复机制，例如未折叠蛋白反应（UPR）和ER相关降解（ERAD）。在溶酶体中，Aβ在与自噬分子相互作用后先于自噬功能障碍。有趣的是，Aβ在抑制端粒酶活性的同时，也是一种转录调节因子。Aβ和p-tau与神经元和神经胶质受体的相互作用均升高炎性分子并引起炎症。本文就Aβ介导的细胞内事件及其在神经退行性变中的广泛作用，以及抗淀粉样蛋白治疗的临床现状作一综述。
Amyloid-β (Aβ) is a dynamic peptide of Alzheimer’s disease (AD) which accelerates the disease progression. At the cell membrane and cell compartments, the amyloid precursor protein (APP) undergoes amyloidogenic cleavage by β- and γ-secretases and engenders the Aβ. In addition, externally produced Aβ gets inside the cells by receptors mediated internalization. An elevated amount of Aβ yields spontaneous aggregation which causes organelles impairment. Aβ stimulates the hyperphosphorylation of tau protein via acceleration by several kinases. Aβ travels to the mitochondria and interacts with its functional complexes, which impairs the mitochondrial function leading to the activation of apoptotic signaling cascade. Aβ disrupts the Ca2+ and protein homeostasis of the endoplasmic reticulum (ER) and Golgi complex (GC) that promotes the organelle stress and inhibits its stress recovery machinery such as unfolded protein response (UPR) and ER-associated degradation (ERAD). At lysosome, Aβ precedes autophagy dysfunction upon interacting with autophagy molecules. Interestingly, Aβ act as a transcription regulator as well as inhibits telomerase activity. Both Aβ and p-tau interaction with neuronal and glial receptors elevate the inflammatory molecules and persuade inflammation. Here, we have expounded the Aβ mediated events in the cells and its cosmopolitan role on neurodegeneration, and the current clinical status of anti-amyloid therapy.
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