Gogia Neha, Chimata Anuradha Venkatakrishnan, Deshpande Prajakta, Singh Aditi, Singh Amit
Department of Biology, University of Dayton, Dayton, OH, USA.
Medical Candidate, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
Neural Regen Res. 2021 Apr;16(4):643-652. doi: 10.4103/1673-5374.295273.
During development, regulation of organ size requires a balance between cell proliferation, growth and cell death. Dysregulation of these fundamental processes can cause a variety of diseases. Excessive cell proliferation results in cancer whereas excessive cell death results in neurodegenerative disorders. Many signaling pathways known-to-date have a role in growth regulation. Among them, evolutionarily conserved Hippo signaling pathway is unique as it controls both cell proliferation and cell death by a variety of mechanisms during organ sculpture and development. Neurodegeneration, a complex process of progressive death of neuronal population, results in fatal disorders with no available cure to date. During normal development, cell death is required for sculpting of an organ. However, aberrant cell death in neuronal cell population can result in neurodegenerative disorders. Hippo pathway has gathered major attention for its role in growth regulation and cancer, however, other functions like its role in neurodegeneration are also emerging rapidly. This review highlights the role of Hippo signaling in cell death and neurodegenerative diseases and provide the information on the chemical inhibitors employed to block Hippo pathway. Understanding Hippo mediated cell death mechanisms will aid in development of reliable and effective therapeutic strategies in future.
在发育过程中,器官大小的调节需要细胞增殖、生长和细胞死亡之间的平衡。这些基本过程的失调会导致多种疾病。细胞过度增殖会导致癌症,而细胞过度死亡会导致神经退行性疾病。迄今为止已知的许多信号通路都在生长调节中发挥作用。其中,进化上保守的Hippo信号通路独具特色,因为它在器官塑造和发育过程中通过多种机制控制细胞增殖和细胞死亡。神经退行性变是神经元群体逐渐死亡的复杂过程,会导致致命疾病,目前尚无有效治疗方法。在正常发育过程中,细胞死亡是器官塑造所必需的。然而,神经元细胞群体中的异常细胞死亡会导致神经退行性疾病。Hippo通路因其在生长调节和癌症中的作用而备受关注,然而,它在神经退行性变等其他功能方面也迅速受到关注。本综述强调了Hippo信号在细胞死亡和神经退行性疾病中的作用,并提供了用于阻断Hippo通路的化学抑制剂的相关信息。了解Hippo介导的细胞死亡机制将有助于未来开发可靠有效的治疗策略。