Unlocking the Complexity of Mitochondrial DNA: A Key to Understanding Neurodegenerative Disease Caused by Injury

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 12; p. 3460
• Main Authors: Singh, Larry N, Kao, Shih-Han, Wallace, Douglas C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.12.2021; MDPI
• Subjects: Alzheimer's disease; Brain Injuries, Traumatic - genetics; Brain Injuries, Traumatic - pathology; DNA, Mitochondrial - genetics; Evolution; Gene expression; Genetic diversity; Genetic factors; Genetic Variation - genetics; Genetics; Genomes; genomics; Humans; Hypotheses; ischaemic stroke; Ischemia; Mitochondria; Mitochondria - genetics; Mitochondrial DNA; Mutation; Neurodegeneration; Neurodegenerative diseases; Phylogenetics; Proteins; Review; Risk Factors; Stroke - genetics; Stroke - pathology; Traumatic brain injury; traumatic brain injury; genomics; ischaemic stroke; genetics; evolution; mitochondria
• ISSN: 2073-4409; 2073-4409
• 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.