Mechanisms of amyloid proteins aggregation and their inhibition by antibodies, small molecule inhibitors, nano-particles, and nano-bodies.
Mechanisms of amyloid proteins aggregation and their inhibition by antibodies, small molecule inhibitors, nano-particles, and nano-bodies.
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DOI：
10.1016/j.ijbiomac.2021.07.056
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发表时间：
2021-07
影响因子：
8.2
通讯作者：
P. Salahuddin;R. H. Khan;Dr Mohammad Furkan;V. Uversky;Z. Islam;M. Fatima
中科院分区：
文献类型：
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作者：
P. Salahuddin;R. H. Khan;Dr Mohammad Furkan;V. Uversky;Z. Islam;M. Fatima
蛋白质错误折叠和聚集可由多种因素诱导，例如显性疾病相关突变、环境条件变化（pH、温度、离子强度、蛋白质浓度、暴露于过渡金属离子、暴露于毒素、翻译后修饰，包括糖化、磷酸化和硫酸化）。错误折叠的中间体与类似的中间体相互作用，并逐渐形成二聚体、寡聚体、原纤维和原纤维。在淀粉样变性中，纤维状聚集体以细胞内包涵体或细胞外斑块（淀粉样蛋白）的形式沉积在组织中。当这种蛋白质存款发生在神经元细胞中时，它引发神经元的变性，并因此导致各种神经变性疾病的表现。已经设计了几种不同类型的分子，并在体外和体内进行了测试，以评估其抗淀粉样蛋白生成的功效。例如，与淀粉样变性相关的蛋白质的天然结构可以通过配体来稳定，抗体可以用于去除斑块，寡聚体特异性抗体A11可以用于去除寡聚体，或者前原纤维聚集体可以通过抗体来去除。考虑到上述观点，在这篇综述中，我们讨论了蛋白质的错误折叠和聚集，蛋白质聚集的机制，负责聚集的因素，以及聚集抑制策略。
Protein misfolding and aggregation can be induced by a wide variety of factors, such as dominant disease-associated mutations, changes in the environmental conditions (pH, temperature, ionic strength, protein concentration, exposure to transition metal ions, exposure to toxins, posttranslational modifications including glycation, phosphorylation, and sulfation). Misfolded intermediates interact with similar intermediates and progressively form dimers, oligomers, protofibrils, and fibrils. In amyloidoses, fibrillar aggregates are deposited in the tissues either as intracellular inclusion or extracellular plaques (amyloid). When such proteinaceous deposit occurs in the neuronal cells, it initiates degeneration of neurons and consequently resulting in the manifestation of various neurodegenerative diseases. Several different types of molecules have been designed and tested bothin vitroandin vivoto evaluate their anti-amyloidogenic efficacies. For instance, the native structure of a protein associated with amyloidosis could be stabilized by ligands, antibodies could be used to remove plaques, oligomer-specific antibody A11 could be used to remove oligomers, or prefibrillar aggregates could be removed by affibodies. Keeping the above views in mind, in this review we have discussed protein misfolding and aggregation, mechanisms of protein aggregation, factors responsible for aggregations, and strategies for aggregation inhibition.