ShcA (Src homologous- collagen homologue), family of adapter proteins, consists of three isoforms which integrate and transduce external stimuli to different signaling networks. ShcA family consists of p46Shc, p52Shc and p66Shc isoforms, characterized by having multiple protein-lipid and protein-protein interaction domains implying their functional diversity. Among the three isoforms p66Shc is structurally different containing an additional CH2 domain which attributes to its dual functionality in cell growth, mediating both cell proliferation and apoptosis. Besides, p66Shc is also involved in different biological processes including reactive oxygen species (ROS) production, cell migration, ageing, cytoskeletal reorganization and cell adhesion. Moreover, the interplay between p66Shc and ROS is implicated in the pathology of various dreadful diseases. Accordingly, here we discuss the recent structural aspects of all ShcA adaptor proteins but are highlighting the case of p66Shc as model isoform. Furthermore, this review insights the role of p66Shc in progression of chronic age-related diseases like neuro diseases, metabolic disorders (non-alcoholic fatty liver, obesity, diabetes, cardiovascular diseases, vascular endothelial dysfunction) and cancer in relation to ROS. We finally conclude that p66Shc might act as a valuable biomarker for the prognosis of these diseases and could be used as a potential therapeutic target.

ShcA（Src同源-胶原同源物），衔接蛋白家族，由三个同工型组成，这些同工型将外部刺激整合并转导至不同的信号网络。ShcA家族由p46Shc，p52Shc和p66Shc亚型组成，其特征是具有多个蛋白质-脂质和蛋白质-蛋白质相互作用域，暗示它们的功能多样性。在这三种同工型中，p66Shc在结构上有所不同，其中包含一个额外的CH2域，该域归因于其在细胞生长中的双重功能，介导细胞增殖和凋亡。此外，p66Shc还参与不同的生物学过程，包括活性氧（ROS）的产生，细胞迁移，衰老，细胞骨架重组和细胞粘附。此外，p66Shc和ROS之间的相互作用与各种可怕疾病的病理学有关。因此，在这里我们讨论所有ShcA衔接蛋白的最新结构方面，但突出了p66Shc作为模型同工型的情况。此外，本综述洞悉了p66Shc在与年龄相关的慢性年龄相关疾病（如神经疾病，代谢性疾病（非酒精性脂肪肝，肥胖症，糖尿病，心血管疾病，血管内皮功能障碍）和与ROS相关的癌症）的进展中的作用。我们最终得出结论，p66Shc可以作为这些疾病预后的有价值的生物标志物，并可以用作潜在的治疗靶标。这篇综述揭示了p66Shc在与年龄相关的慢性年龄相关疾病（如神经疾病，代谢性疾病（非酒精性脂肪肝，肥胖症，糖尿病，心血管疾病，血管内皮功能障碍）和癌症）进展中的作用。我们最终得出结论，p66Shc可以作为这些疾病预后的有价值的生物标志物，并可以用作潜在的治疗靶标。这篇综述揭示了p66Shc在与年龄相关的慢性年龄相关疾病（如神经疾病，代谢性疾病（非酒精性脂肪肝，肥胖，糖尿病，心血管疾病，血管内皮功能障碍）和癌症）进展中的作用。我们最终得出结论，p66Shc可以作为这些疾病预后的有价值的生物标志物，并可以用作潜在的治疗靶标。