以生物資訊方法學探究癌症與腦損傷之相關訊息傳遞路徑

Traumatic brain injury (TBI) is a major contributor to illness and death on a global scale. Despite ongoing research efforts, advancements in the field have been hindered by the diverse range of patients and injuries, making prevention, diagnosis, and treatment of TBI a substantial challenge. TBI-induced oxidative stress significantly contributes to secondary brain damage progression that can exacerbate later neurodegenerative diseases. Despite the lack of FDA-approved treatment therapies, antioxidants have shown promise in mitigating the harmful effects of oxidative stress and reactive oxygen species (ROS) in various pre-clinical studies.
Previous research outcomes have suggested that HDAC inhibitors can modulate gene expression through histone acetylation which has raised optimism for their potential therapeutic applications beyond cancer treatment, particularly in the field of regenerative medicine and neurological disorders. Additionally, acetylated tubulin has been reported to be one of the characteristics of stabilized microtubules which is crucial for maintaining the proper function and morphology of eukaryotic cells. HDAC6, which is a microtubule-associated deacetylase, was selected as the main subject of this research instead of other HDACs in the context of TBI.
In our previous work, we investigated the effects of a newly developed selective HDAC6 inhibitor called MPT0B241 on TBI mice. The results demonstrated that this compound showed significant promise in improving the outcomes of TBI, particularly in mitigating the consequences of neurodegeneration and enhancing antioxidant capacity as suggested by RNA-sequencing analysis results. Therefore, in this work, our objective is to examine the antioxidant capacity and protective effects of the three dual EZH2/HDAC6 inhibitor compounds in the same series, namely MPT0B241, MPT0B244, and MPT0B252, against TBI-induced oxidative stress. RNA sequencing, followed by relevant bioinformatics analysis will be conducted later to further investigate the differentially expressed genes encoding for such functions. By gaining a better understanding of the pharmacological mechanisms responsible for the antioxidant and neuroprotective functions of dual EZH2/HDAC6 inhibitors under TBI-induced oxidative stress, we hope to contribute to further improving the utilization of alternative treatment options for the long-term management of TBI.