Center for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Resuscitation Science Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Cells. 2021 Dec 8;10(12):3460. doi: 10.3390/cells10123460.
Neurodegenerative disorders that are triggered by injury typically have variable and unpredictable outcomes due to the complex and multifactorial cascade of events following the injury and during recovery. Hence, several factors beyond the initial injury likely contribute to the disease progression and pathology, and among these are genetic factors. Genetics is a recognized factor in determining the outcome of common neurodegenerative diseases. The role of mitochondrial genetics and function in traditional neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, is well-established. Much less is known about mitochondrial genetics, however, regarding neurodegenerative diseases that result from injuries such as traumatic brain injury and ischaemic stroke. We discuss the potential role of mitochondrial DNA genetics in the progression and outcome of injury-related neurodegenerative diseases. We present a guide for understanding mitochondrial genetic variation, along with the nuances of quantifying mitochondrial DNA variation. Evidence supporting a role for mitochondrial DNA as a risk factor for neurodegenerative disease is also reviewed and examined. Further research into the impact of mitochondrial DNA on neurodegenerative disease resulting from injury will likely offer key insights into the genetic factors that determine the outcome of these diseases together with potential targets for treatment.
由于损伤后和恢复期间事件的复杂和多因素级联,由损伤引发的神经退行性疾病通常具有可变和不可预测的结果。因此,除了初始损伤之外,还有几个因素可能导致疾病进展和病理学,其中包括遗传因素。遗传学是决定常见神经退行性疾病结果的公认因素。线粒体遗传学和功能在传统神经退行性疾病(如阿尔茨海默病和帕金森病)中的作用已得到充分确立。然而,对于创伤性脑损伤和缺血性中风等损伤引起的神经退行性疾病,线粒体遗传学的了解要少得多。我们讨论了线粒体 DNA 遗传学在损伤相关神经退行性疾病进展和结果中的潜在作用。我们提供了一份理解线粒体遗传变异的指南,以及量化线粒体 DNA 变异的细微差别。还审查和检查了支持线粒体 DNA 作为神经退行性疾病风险因素的证据。进一步研究线粒体 DNA 对损伤引起的神经退行性疾病的影响可能会为决定这些疾病结果的遗传因素以及治疗的潜在靶点提供关键见解。