Unveiling the Significance of Peroxiredoxin 6 in Central Nervous System Disorders
Abstract
:1. Introduction
2. Structure of Prdx6
3. Enzyme Activities and Function of Prdx6
4. Prdx6 Expression in the CNS
5. Prdx6 and CNS Diseases
5.1. Alzheimer’s Disease (AD)
Tissues | Species | Expression Level | Expression Tissue | Function | Reference |
---|---|---|---|---|---|
Postmortem brain | Human | ↑ | midfrontal cortex, cingulate, hippocampus, and amygdala | Prdx6 plays an anti-oxidant role in AD | [43] |
Postmortem brain (female) | Human | ↑ | superior frontal gyrus | N/A | [46] |
rpAD postmortem brain | Human | ↓ | hippocampus | N/A | [47] |
Postmortem brain | Human | no change | frontal cortex and cerebellum | Prdx6 did not show significant changes in the brains of AD patients and possibly has no critical role in cellular defense against oxidative stress. | [50] |
Postmortem brain | Human | ↑ | hippocampus | The increased expression of Prdx6 in AD was closely related to the degree of oxidative stress. | [51] |
Tissues | Species | Expression Level | Expression Tissue | Function | Reference |
---|---|---|---|---|---|
APP/PS1 Prdx6 Tg female mice | Mice | ↑ | cortex and hippocampus | The upregulation of Prdx6 in AD mice can attenuate Aβ pathology. | [6] |
3xTg mice | Mice | no change | hippocampus | Prdx6 was not associated with cumulative oxidative stress in animal models of neurodegenerative disease. | [49] |
PS2 (N141I) Tg mice | Mice | ↓ | lung | The PS2 mutation inhibits the aiPLA2 activity of Prdx6 through the γ-secretase cleavage mechanism to suppress lung-tumor development. | [53] |
Aβ1–42-infused Prdx6 transgenic mice | Mice | ↑ | cortex and hippocampus | The overexpression of Prdx6 in AD mice promotes amyloidosis and increases oxidative stress, thereby expediting the progression of AD. | [54] |
Tau (P301S) Tg mice | Mice | ↑ | anterior horn of the spinal cord | Prdx6 functions as a neuroprotective mechanism against tau toxicity. | [56] |
Aβ25–35-treated BV2 cells | Mice | ↑ | N/A | Prdx6 is protective against oxidative stress in microglia and synergistically maintains the transition to a chronic neuroinflammatory phenotype, reinforcing the role of Prdx6 in AD | [57] |
Aβ1–42-infused rat | Rat | ↑ | hippocampus | N/A | [48] |
Aβ1–42-induced rat primary neuron | Rat | ↓ | N/A | Thiacremonone influences Prdx6 expression levels and oxidative stress, thereby protecting against amyloidosis and memory dysfunction and inhibiting the development and progression of AD. | [55] |
Aβ25–35-treated rat PC12 cells | Rat | ↑ | N/A | Prdx6 can slow the progression of AD and limit the extent of AD-induced neuronal cell death. | [58] |
5.2. Parkinson’s Disease (PD)
5.3. Cerebral Ischemia
5.4. Spinal Cord Injury (SCI)
5.5. Traumatic Brain Injury (TBI)
5.6. Prion Disease
5.7. Multiple Sclerosis (MS)
5.8. Amyotrophic Lateral Sclerosis (ALS)
5.9. Gliomas
5.10. Epilepsy
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Tissues | Species | Expression Level | Expression Tissue | Function | Reference |
---|---|---|---|---|---|
Postmortem brain | Human | ↑ | gray and white matter | Prdx6 was upregulated in certain cells to respond to oxidative stress in PD. | [62] |
HeLa cells with CCCP-induced GFP-Parkin overexpression | Human | ↑ | N/A | Prdx6 controls ROS homeostasis during the initial phase of PINK1-Parkin-mediated mitotic phagocytosis. | [67] |
HEK293 cells with inducible Parkin expression | Human | ↓ | N/A | Prdx6 is a potential substrate of the Parkin. | [68] |
Tissues | Species | Expression Level | Expression Tissue | Function | Reference |
---|---|---|---|---|---|
Parkin−/− mice | mice | ↓ | ventral midbrain | N/A | [63] |
MPTP-induced mice and 6-OHDA-induced rats | mice/rats | ↑ | striatum | aiPLA2 inhibitor QNC protects against 6-OHDA and MPTP-induced dopaminergic neurotoxicity. | [64] |
Prdx6 Tg mice in MPTP administration | mice | ↑ | substantia nigra and striatum | The aiPLA2 activity of Prdx6 was increased after MPTP administration in the Prdx6 transgenic mice, which results in a greater loss of dopaminergic neurons and increased behavioral damage. | [65] |
Models | Species | Expression Level | Expression Tissue | Function | Reference |
---|---|---|---|---|---|
TET-1 MCAO | mouse | ↑ | hippocampus | In TET-1 mice perfused for 7 days after 30 min of MCAO, an increased expression of perivascular Prdx6 in the hippocampus may lead to neuronal apoptosis, glial activation, and blood–brain barrier disruption. | [73] |
Tlr2−/−; Tlr4−/− MCAO | mouse | ↑ | N/A | Prdx6 promotes neuronal cell death by activating Toll-like receptor 2 (TLR2) and TLR4 and inducing macrophages to express inflammatory cytokines, including IL-23. | [80] |
MCAO | rat | ↑ | N/A | The MCAO model induced an abnormal increased expression of Prdx6, but after human brain endothelial cell transplantation, Prdx6 levels in the MCAO models decreased. | [71] |
Stroke with heat-induced brain injury in the left anterior cortex | rat | ↑ | hippocampus | A sustained upregulation of Prdx6 expression may help protect hippocampal neurons from oxidative stress in a rat model of stroke (localized heat-induced brain injury in the left anterior cortical tectum). | [75] |
MCAO | rat | ↑ | peri-infarct cortex | Prdx6 is involved in the inhibition of curcumin-induced oxidative stress during I/R, and the upregulation of Prdx6 by curcumin attenuates ischemic oxidative damage via SP1 in post-stroke rats. | [76] |
MCAO | rat | ↓ | cerebral cortex | In ischemic brain injury, Prdx6 was increased with a melatonin treatment to protect neuronal cells from ischemic damage. | [78] |
MCAO | rat | ↑ | cortex | Prdx6 may be an important target for immunomodulation and neuroinflammation after ischemic stroke. Prdx6 released from ischemic cells acts as an endogenous ligand for TLR4 and initiates destructive immune responses in ischemic brains. | [79] |
OGD/R and MCAO | rat | ↑ | cortex | The aiPLA2 activity of Prdx6 may play a key role in cerebral ischemia/reperfusion injury by regulating TLR2/4, which induces the production of NF-κB, iNOS, and COX-2, and promote neuroinflammation. | [80] |
MCAO | rat | ↑ | cerebral cortex | Prdx6 knockdown exacerbates cerebral ischemia-reperfusion injury by enhancing PINK1/PARKIN pathway-mediated mitophagy, an effect that increases neuronal apoptosis. | [81] |
OGD/R and MCAO | rat | ↑ | cortex | Prdx6 is upregulated by 4-HBA to protect neurons from cerebral ischemic injury, possibly through the PI3K/Akt pathway. | [83] |
Cutting the inner capsule of pig tissue | pig | ↑ | N/A | Prdx6 is involved in neuroprotective mechanisms after stroke, such as compensating for oxidative stress. | [72] |
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Xue, M.; Huang, X.; Zhu, T.; Zhang, L.; Yang, H.; Shen, Y.; Feng, L. Unveiling the Significance of Peroxiredoxin 6 in Central Nervous System Disorders. Antioxidants 2024, 13, 449. https://doi.org/10.3390/antiox13040449
Xue M, Huang X, Zhu T, Zhang L, Yang H, Shen Y, Feng L. Unveiling the Significance of Peroxiredoxin 6 in Central Nervous System Disorders. Antioxidants. 2024; 13(4):449. https://doi.org/10.3390/antiox13040449
Chicago/Turabian StyleXue, Min, Xiaojie Huang, Tong Zhu, Lijun Zhang, Hao Yang, Yuxian Shen, and Lijie Feng. 2024. "Unveiling the Significance of Peroxiredoxin 6 in Central Nervous System Disorders" Antioxidants 13, no. 4: 449. https://doi.org/10.3390/antiox13040449
APA StyleXue, M., Huang, X., Zhu, T., Zhang, L., Yang, H., Shen, Y., & Feng, L. (2024). Unveiling the Significance of Peroxiredoxin 6 in Central Nervous System Disorders. Antioxidants, 13(4), 449. https://doi.org/10.3390/antiox13040449