Navarrete Meaghan, Zhou Yi
Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, United States.
Front Mol Neurosci. 2022 Mar 14;15:857495. doi: 10.3389/fnmol.2022.857495. eCollection 2022.
Schizophrenia is a debilitating mental disorder that affects approximately 1% of the world population, yet the disorder is not very well understood. The genetics of schizophrenia is very heterogenous, making it hard to pinpoint specific alterations that may cause the disorder. However, there is growing evidence from human studies suggesting a link between alterations in the 14-3-3 family and schizophrenia. The 14-3-3 proteins are abundantly expressed in the brain and are involved in many important cellular processes. Knockout of 14-3-3 proteins in mice has been shown to cause molecular, structural, and behavioral alterations associated with schizophrenia. Thus, 14-3-3 animal models allow for further exploration of the relationship between 14-3-3 and schizophrenia as well as the study of schizophrenia pathology. This review considers evidence from both human and animal model studies that implicate the 14-3-3 family in schizophrenia. In addition, possible mechanisms by which alterations in 14-3-3 proteins may contribute to schizophrenia-like phenotypes such as dopaminergic, glutamatergic, and cytoskeletal dysregulations are discussed.
精神分裂症是一种使人衰弱的精神障碍，影响着全球约1%的人口，但人们对这种疾病的了解并不深入。精神分裂症的遗传学非常复杂，难以确定可能导致该疾病的具体改变。然而，越来越多的人体研究证据表明，14-3-3家族的改变与精神分裂症之间存在联系。14-3-3蛋白在大脑中大量表达，并参与许多重要的细胞过程。在小鼠中敲除14-3-3蛋白已被证明会导致与精神分裂症相关的分子、结构和行为改变。因此，14-3-3动物模型有助于进一步探索14-3-3与精神分裂症之间的关系以及精神分裂症病理学研究。这篇综述考虑了来自人体和动物模型研究的证据，这些证据表明14-3-3家族与精神分裂症有关。此外，还讨论了14-3-3蛋白改变可能导致类似精神分裂症表型的潜在机制，如多巴胺能、谷氨酸能和细胞骨架失调。
