Evidence for the Role of Mitochondrial DNA Release in the Inflammatory Response in Neurological Disorders
Abstract
:1. Introduction
2. Mechanisms of Mitochondrial DNA Release
2.1. mtDNA Release in Response to Cellular Stress
2.2. mtDNA Release as a Pillar for Immune and Inflammatory Processes
3. Analysis of a Potential Link between Mitochondrial Dysfunction and Progression of Neuronal Disease
3.1. Neurodegenerative Diseases
3.1.1. Amyotrophic Lateral Sclerosis (ALS)
mtDNA Release in ALS
Aberrant Mitochondrial Function in ALS
Inflammatory and Immune Responses in ALS
3.1.2. Parkinson’s Disease (PD)
mtDNA Release in PD
Aberrant Mitochondrial Function in PD
Inflammatory and Immune Responses in PD
3.1.3. Alzheimer’s Disease
mtDNA Release in AD
Aberrant Mitochondrial Function in AD
Inflammatory and Immune Responses in AD
3.2. Neuropsychiatric Disorders
3.2.1. Major Depressive Disorder (MDD)
mtDNA Release in MDD
Aberrant Mitochondrial Function in MDD
Inflammatory and Immune Responses in MDD
4. Conclusions and Outlook
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
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Disease | Species | Sample | Finding | Ref. |
---|---|---|---|---|
Neurodegenerative diseases | ||||
MS | H. sapiens | CSF samples of MS patients | Association between lower ccf-mtDNA and MS and neurodegeneration | [57] |
MS | H. sapiens | MS patients’ blood plasma samples | Increased ccf-mtDNA in MS patients compared to healthy patients | [58,59] |
MS | H. sapiens | MS patients’ CSF samples | Increased ccf-mtDNA in CSF of MS patients compared to cognitively healthy patients | [60] |
MS | H. sapiens | Relapsing-remitting MS patients’ peripheral blood samples | Decreased ccf-mtDNA levels in MS patients’ when compared to healthy patients | [61] |
PD | H. sapiens | CSF samples from PD patients | Reduced ccf-mtDNA in CSF from PD patients compared to healthy subjects | [62] |
PD | H. sapiens | CSF samples from PD patients | Significant reduction in ccf-mtDNA in PD patients Reduction in ccf-mtDNA associated with type and duration of treatment | [63] |
AD | H. sapiens | CSF samples from preclinical AD patients | Lower ccf-mtDNA levels in CSF of preclinical AD patients (several studies failed to replicate results) | [64] |
ALS | M. musculus | In vivo study of aberrant TDP-43 transgenic mice | TDP-43 Caused mtDNA release to the cytoplasm via the mPTP | [29] |
ALS | H. Sapiens | ALS spinal cord neuron cell line | ALS spinal cord neurons showed significant reductions in mtDNA-cn and mitochondrial gene deletions | [65] |
Neuropsychiatric diseases | ||||
Addiction | H. sapiens | Methamphetamine-addiction model in human dopaminergic neuroblastoma SH-SY5Y cell line | Decrease in mtDNA-cn Apoptosis after 48 h of treatment | [66] |
Addiction | M. musculus | Peripheral blood from murine model of morphine addiction Peripheral blood from heroin addiction patients | Decrease in mtDNA-cn in hippocampi; Melatonin-dosage restored mtDNA-cn | [67] |
Anxiety | H. sapiens | Serum samples from a middle-aged cohort | Increased ccf-mtDNA levels with introduction of negative mood stimulus | [68] |
MDD | H. sapiens | Plasma samples from suicide attempters | Increased levels of ccf-mtDNA | [69] |
MDD | H. sapiens | Plasma samples from unmedicated MDD patients | Elevated ccf-mtDNA levels compared to healthy subjects; No significant difference in peripheral blood mononuclear cells’ mtDNA-cn | [70] |
SZ | H. sapiens | Patient blood plasma samples | Increase in ccf-mtDNA in SZ patients; mtDNA release because of exacerbated apoptosis | [71] |
SZ BD | H. sapiens | Whole-blood samples of screened patients | Increasing age and psychosis severity correlated with decreasing ccf-mtDNA levels; Risperidone treatments found to have a reducing effect on ccf-mtDNA at concentrations simulating clinical target level in plasma, but not at concentrations simulating CSF or brain interstitial target level | [72] |
BD type I (BD-I) | H. sapiens | BD-I patients’ leukocyte samples | Negative association between number of manic-episode relapses and mtDNA-cn | [73] |
BD | H. sapiens | Serum samples from an adolescent cohort | No significant difference in ccf-mtDNA levels between groups; Increase in serum lactate levels for adolescents diagnosed with BD | [74] |
BD | H. sapiens | Plasma samples from MDD patients | MDD patients showed lower plasma mtDNA levels than healthy patients | [75] |
BD | H. sapiens | Serum samples from BD patients | Higher levels of ccf-mtDNA in BD patients | [76] |
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Moya, G.E.; Rivera, P.D.; Dittenhafer-Reed, K.E. Evidence for the Role of Mitochondrial DNA Release in the Inflammatory Response in Neurological Disorders. Int. J. Mol. Sci. 2021, 22, 7030. https://doi.org/10.3390/ijms22137030
Moya GE, Rivera PD, Dittenhafer-Reed KE. Evidence for the Role of Mitochondrial DNA Release in the Inflammatory Response in Neurological Disorders. International Journal of Molecular Sciences. 2021; 22(13):7030. https://doi.org/10.3390/ijms22137030
Chicago/Turabian StyleMoya, Gonzalo E., Phillip D. Rivera, and Kristin E. Dittenhafer-Reed. 2021. "Evidence for the Role of Mitochondrial DNA Release in the Inflammatory Response in Neurological Disorders" International Journal of Molecular Sciences 22, no. 13: 7030. https://doi.org/10.3390/ijms22137030