Glutathione Depletion and MicroRNA Dysregulation in Multiple System Atrophy: A Review
Abstract
:1. Introduction
2. An Overview of MSA
2.1. Clinical Classification of MSA
2.2. Pathological Features of MSA
2.3. Distinction between MSA and Lewy Body Diseases
3. Genes Associated with MSA Features
Gene Name | Encoding Protein | Physiological Function | Pathology | Related NDs [69] |
---|---|---|---|---|
SNCA | α-synuclein | regulation of synaptic vesicles and neurotransmitter release | inclusion formation | PD, LBD |
COQ2 | polyprenyl transferase | catalyzing coenzyme Q10 biosynthesis | coenzyme Q10 deficiency, followed by mitochondrial dysfunction | PD |
MAPT | microtubule-associated protein tau | formation and stabilization of axonal microtubules | tau accumulation | AD, FTD, PD |
LRRK2 | leucine rich-repeat kinase 2 | involved in neuronal plasticity, autophagy, and vesicle trafficking | associated with pathologies of α-syn | PD |
GBA1 | β-glucocerebrosidase | hydrolysis of glucosylceramide and glucosylsphingosine | α-syn accumulation | AD, FTD, PD |
TBP | TATA-box binding protein | component of the eukaryotic transcription initiation machinery | formation of aggregates | PD, HD |
CHCHD2 | coiled-coil-helix-coiled-coil-helix domain containing 2 | regulating electron flow in the mitochondrial electron transport chain | mitochondrial dysfunction | AD, FTD, PD, ALS, |
c9orf72 | chromosome 9 open reading frame 72 | regulation of autophagy and vesicular trafficking | formation of aggregates | FTD, ALS |
ASCT1 | alanine/serine/cysteine/threonine transporter 1 | uptake of neutral amino acids | enhanced oxidative stress | No data |
EAAC1 | excitatory amino acid carrier 1 | cysteine uptake | GSH depletion, followed by oxidative stress | No data |
TauT | taurine transporter | taurine uptake | taurine depletion, followed by oxidative stress | No data |
NOVA1 | neuro-oncological ventral antigen-1 | alternative splicing, involved in the formation and activity of the synapses | autoantigen in paraneoplastic opsoclonus myoclonus ataxia | No data |
Oct1 | organic cation transporter1 | Translocation of organic cations across the blood–brain barrier | unknown | No data |
4. The Association between GSH Dysregulation and MSA
4.1. GSH Levels in Patients with MSA
4.2. Possible Association of the Enzymes for GSH Synthesis and Metabolism with MSA
4.3. Association between Transporters Related to GSH Biosynthesis and MSA
5. The Association of miRNA Dysregulation and MSA Pathology
5.1. Molecular Mechanisms of miRNA Biogenesis
5.2. Dysregulation of Genes and miRNAs in Patients with MSA
5.3. Candidate miRNA Biomarkers for MSA
6. Prospective for Diagnosis and Treatment of NDs including MSA
7. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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miRNA | Number of Reports | Detection Area | Features | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Serum [112,113,118] | Plasma [114,119] | CSF [119] | Cerebellum [116,117] | Pons [116] | Striatum [115] | Frontal Cortex [18] | Related NDs [133,134] | Regulatory Function [135] | ||
hsa-miR-24-3p | 6 | ↑↑↑ | ↓ | n.d. | n.d. | n.d. | ↑ | ↑ | AD, PD, HD | regulation of neuronal differentiation |
hsa-miR-19b-3p | 4 | ↑ | ↓ | ↑ | n.d. | n.d. | n.d. | ↑ | AD, PD | regulation of neural proliferation |
hsa-miR-25-3p | 4 | ↑↑ | n.d. | n.d. | n.d. | n.d. | ↑ | ↑ | AD, PD | aggravating Aβ -induced neuron injury |
hsa-miR-92a-3p | 4 | ↑ | n.d. | ↓ | n.d. | n.d. | ↑ | ↑ | AD, ALS | aggravating oxidative stress |
hsa-let-7b-5p | 3 | ↑↑ | n.d. | n.d. | n.d. | n.d. | ↑ | n.d. | AD, PD, ALS | regulation of neuronal apoptosis |
hsa-miR-15b-5p | 3 | ↑ | ↓ | n.d. | n.d. | n.d. | n.d. | ↑ | AD, ALS | protection against neuronal damage |
hsa-miR-16-5p | 3 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | AD, PD, ALS | associated with Aβ deposition |
hsa-miR-17-5p | 3 | ↑↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | AD, PD | protection against neurotoxicity |
hsa-miR-23a-3p | 3 | ↑ | n.d. | n.d. | n.d. | ↑ | n.d. | ↑ | ALS, HD | associated with neuronal apoptosis |
hsa-miR-93-5p | 3 | ↑ | n.d. | n.d. | n.d. | n.d. | ↑ | ↑ | AD, ALS | inhibition of microglial activation and inflammatory reaction |
hsa-miR-99a-5p | 3 | ↑ | n.d. | ↓ | n.d. | n.d. | n.d. | ↑ | AD, PD | localized at post-synaptic densities in forebrain |
hsa-miR-106a-5p | 3 | ↑↑ | n.d. | ↓ | n.d. | n.d. | n.d. | n.d. | PD | regulation of neurogenesis |
hsa-mIR-124-3p | 3 | n.d. | n.d. | n.d. | n.d. | ↓ | ↓ | ↑ | AD, ALS | regulation of neuronal development |
hsa-miR-129-5p | 3 | n.d. | n.d. | n.d. | ↓↓ | ↓ | n.d. | n.d. | AD, PD, ALS | regulation of apoptosis and neuroinflammation |
hsa-miR-186-5p | 3 | ↑ | n.d. | n.d. | n.d. | n.d. | ↑ | ↑ | AD, ALS | suppression of BACE1, enzyme for Aβ generation |
hsa-miR-484 | 3 | ↑ | n.d. | n.d. | ↓↓ | n.d. | n.d. | n.d. | no data | regulation of neuronal apoptosis |
hsa-let-7a-5p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | AD, PD, ALS | differentiation of neural stem cells |
hsa-let-7c-5p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | PD | regulation of neural stem cell differentiation |
hsa-let-7d-5p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | AD, PD, ALS | regulation of neural cell fate and neurogenesis |
hsa-let-7i-5p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | AD, PD, ALS | protection against brain damage |
hsa-miR-20a-5p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | AD | protection against neurotoxicity |
hsa-miR-21-5p | 2 | n.d. | n.d. | n.d. | n.d. | ↑ | n.d. | ↑ | AD, PD | protection against neuronal damage |
hsa-miR-27a-3p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | AD | regulator of tight junction at brain endothelium |
hsa-miR-30b-5p | 2 | n.d. | ↑ | n.d. | n.d. | ↑ | n.d. | n.d. | AD, PD, ALS | protection against neurotoxicity |
hsa-miR-30d-5p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | AD, PD | regulation of neuronal autophagy and apoptosis |
hsa-miR-96-5p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | PD, ALS | regulation of neuronal glutathione level |
hsa-miR-100-5p | 2 | n.d. | n.d. | ↓ | n.d. | n.d. | ↑ | n.d. | AD | leading microglial accumulation |
hsa-miR-103a-3p | 2 | ↑↑ | n.d. | n.d. | n.d. | n.d. | n.d. | n.d. | AD, PD, ALS | promotion neural outgrowth |
hsa-miR-107 | 2 | ↑↑ | n.d. | n.d. | n.d. | n.d. | n.d. | n.d. | AD | prevention of Aβ -induced neurotoxicity |
hsa-miR-127-3p | 2 | n.d. | n.d. | n.d. | ↓ | ↓ | n.d. | n.d. | AD | regulation of neuronal autophagy |
hsa-miR-129-2-3p | 2 | n.d. | n.d. | n.d. | ↓ | ↓ | n.d. | n.d. | no data | targeting GABAA receptor to protect epilepsy |
hsa-miR-130a-3p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | PD, ALS | promotion of the neuronal differentiation |
hsa-miR-132-3p | 2 | n.d. | n.d. | n.d. | ↓↓ | n.d. | n.d. | n.d. | AD, PD, ALS, HD | regulation of neuronal differentiation, maturation and functioning |
hsa-miR-138-5p | 2 | n.d. | n.d. | n.d. | ↓ | ↓ | n.d. | n.d. | AD | control of hippocampal interneuron function |
hsa-miR-142-5p | 2 | n.d. | n.d. | n.d. | ↑ | n.d. | n.d. | ↑ | AD, PD | improvement of neural differentiation |
hsa-miR-155-5p | 2 | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | ↑ | AD, ALS | pro-inflammatory mediator of the central nervous system |
hsa-miR-181a-5p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | ↑ | n.d. | AD, PD | promotion of neuronal degeneration |
hsa-mIR-185-5p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | ↑ | n.d. | AD | inhibition of neuronal autophagy and apoptosis |
hsa-miR-191-5p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | AD | alleviation of microglial cell injury |
hsa-miR-219a-2-3p | 2 | n.d. | n.d. | n.d. | ↓ | n.d. | ↑ | n.d. | no data | unknown |
hsa-miR-339-5p | 2 | ↓↓ | n.d. | n.d. | n.d. | n.d. | n.d. | n.d. | AD | negative regulation of BACE1 activity |
hsa-miR-371b-3p | 2 | n.d. | ↑ | n.d. | n.d. | ↓ | n.d. | n.d. | no data | unknown |
hsa-miR-380-3p | 2 | ↓ | n.d. | n.d. | ↓ | n.d. | n.d. | n.d. | AD | enhancement of neurotoxicity |
hsa-miR-425-5p | 2 | ↑ | n.d. | n.d. | n.d. | n.d. | n.d. | ↑ | AD, ALS | promotion of neuronal necroptosis |
hsa-miR-486-5p | 2 | ↑ | n.d. | n.d. | ↓ | n.d. | n.d. | n.d. | ALS | targeting NeuroD6, scavenger gene of ROS |
hsa-mIR-539-5p | 2 | n.d. | n.d. | n.d. | ↓ | n.d. | ↓ | n.d. | no data | inhibition of inflammatory response of neuron |
hsa-miR-1233-3p | 2 | n.d. | n.d. | n.d. | ↓ | ↓ | n.d. | n.d. | no data | unknown |
hsa-miR-1290 | 2 | n.d. | n.d. | n.d. | ↑ | ↑ | n.d. | n.d. | no data | regulation of neuronal differentiation |
hsa-miR-3663-5p | 2 | n.d. | n.d. | n.d. | ↓ | ↓ | n.d. | n.d. | no data | unknown |
hsa-miR-4428 | 2 | n.d. | n.d. | n.d. | ↑ | ↑ | n.d. | n.d. | no data | unknown |
hsa-miR-4440 | 2 | n.d. | n.d. | n.d. | ↓ | ↓ | n.d. | n.d. | no data | unknown |
hsa-miR-4726-3p | 2 | n.d. | ↓ | n.d. | n.d. | ↓ | n.d. | n.d. | no data | unknown |
hsa-miR-4739 | 2 | n.d. | n.d. | n.d. | ↓ | ↓ | n.d. | n.d. | no data | unknown |
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Kinoshita, C.; Kubota, N.; Aoyama, K. Glutathione Depletion and MicroRNA Dysregulation in Multiple System Atrophy: A Review. Int. J. Mol. Sci. 2022, 23, 15076. https://doi.org/10.3390/ijms232315076
Kinoshita C, Kubota N, Aoyama K. Glutathione Depletion and MicroRNA Dysregulation in Multiple System Atrophy: A Review. International Journal of Molecular Sciences. 2022; 23(23):15076. https://doi.org/10.3390/ijms232315076
Chicago/Turabian StyleKinoshita, Chisato, Noriko Kubota, and Koji Aoyama. 2022. "Glutathione Depletion and MicroRNA Dysregulation in Multiple System Atrophy: A Review" International Journal of Molecular Sciences 23, no. 23: 15076. https://doi.org/10.3390/ijms232315076