In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release f...In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.展开更多
研究证实,在基因的表观遗传调控中DNA甲基化起着至关重要的作用。而DNA甲基转移酶(DNMT)催化DNA甲基化,这是DNA甲基化模式形成和保持的必要条件。在哺乳动物细胞中,有三种关键的DNMT负责着不同的任务。首先是DNMT1,负责维持DNA的甲基化...研究证实,在基因的表观遗传调控中DNA甲基化起着至关重要的作用。而DNA甲基转移酶(DNMT)催化DNA甲基化,这是DNA甲基化模式形成和保持的必要条件。在哺乳动物细胞中,有三种关键的DNMT负责着不同的任务。首先是DNMT1,负责维持DNA的甲基化状态,保持细胞功能正常运转。而另外两种则是DNMT3a和DNMT3b,它们则负责推动DNA从头开始的甲基化过程。目前,急性髓系白血病(AML)的病因仍无法完全阐明。通过研究发现,异常的表观遗传学变化与AML的发病密切相关。深入探讨DNA甲基化与AML之间的联系,将为治疗这种疾病和开发新药物提供关键的分子靶点。这一领域的突破将为医学界带来新的希望,为患者提供更有效的治疗方案。Research has confirmed that DNA methylation plays a crucial role in the epigenetic regulation of genes. DNA methyltransferase (DNMT) catalyzes DNA methylation, which is a necessary condition for the formation and maintenance of DNA methylation patterns. In mammalian cells, there are three key DNMTs responsible for different tasks. Firstly, DNMT1 is responsible for maintaining the methylation status of DNA and ensuring the normal functioning of cells. The other two are DNMT3a and DNMT3b, which are responsible for driving the DNA methylation process from scratch. At present, the etiology of acute myeloid leukemia (AML) cannot be fully elucidated. Through research, it has been found that abnormal epigenetic changes are closely related to the onset of AML. Exploring the relationship between DNA methylation and AML in depth will provide key molecular targets for the treatment of this disease and the development of new drugs. Breakthroughs in this field will bring new hope to the medical community and provide more effective treatment options for patients.展开更多
基金supported by the National Natural Science Foundation of China,No.81971269 (to DP)the Science and Technology Commission of Shanghai,No.YDZX20213100001003 (to DP)。
文摘In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.
文摘研究证实,在基因的表观遗传调控中DNA甲基化起着至关重要的作用。而DNA甲基转移酶(DNMT)催化DNA甲基化,这是DNA甲基化模式形成和保持的必要条件。在哺乳动物细胞中,有三种关键的DNMT负责着不同的任务。首先是DNMT1,负责维持DNA的甲基化状态,保持细胞功能正常运转。而另外两种则是DNMT3a和DNMT3b,它们则负责推动DNA从头开始的甲基化过程。目前,急性髓系白血病(AML)的病因仍无法完全阐明。通过研究发现,异常的表观遗传学变化与AML的发病密切相关。深入探讨DNA甲基化与AML之间的联系,将为治疗这种疾病和开发新药物提供关键的分子靶点。这一领域的突破将为医学界带来新的希望,为患者提供更有效的治疗方案。Research has confirmed that DNA methylation plays a crucial role in the epigenetic regulation of genes. DNA methyltransferase (DNMT) catalyzes DNA methylation, which is a necessary condition for the formation and maintenance of DNA methylation patterns. In mammalian cells, there are three key DNMTs responsible for different tasks. Firstly, DNMT1 is responsible for maintaining the methylation status of DNA and ensuring the normal functioning of cells. The other two are DNMT3a and DNMT3b, which are responsible for driving the DNA methylation process from scratch. At present, the etiology of acute myeloid leukemia (AML) cannot be fully elucidated. Through research, it has been found that abnormal epigenetic changes are closely related to the onset of AML. Exploring the relationship between DNA methylation and AML in depth will provide key molecular targets for the treatment of this disease and the development of new drugs. Breakthroughs in this field will bring new hope to the medical community and provide more effective treatment options for patients.
