Progress in research on the role of Omi/HtrA2 in neurological diseases

Abstract Omi/HtrA2 is a serine protease present in the mitochondrial space. When stimulated by external signals, HtrA2 is released into the mitochondrial matrix where it regulates cell death through its interaction with apoptotic and autophagic signaling pathways. Omi/HtrA2 is closely related to the pathogenesis of neurological diseases, such as neurodegeneration and hypoxic ischemic brain damage. Here, we summarize the biological characteristics of Omi/HtrA2 and its role in neurological diseases, which will provide new hints in developing Omi/HtrA2 as a therapeutic target for neurological diseases.

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In Vivo and in Vitro Evaluation of the Anti-inflammatory Effect of Thymoquinone Toward Ischemic Brain Injury Alleviation via Nrf2/HO-1 Pathway

10.21203/rs.3.rs-93479/v1 ◽

2020 ◽

Author(s):

Nashwa Amin ◽

Xiaoxue Du ◽

Shijia Chen ◽

Qiannan Ren ◽

Azhar Badry ◽

...

Keyword(s):

Cell Death ◽

Cerebral Ischemia ◽

Brain Damage ◽

Ischemic Brain Injury ◽

Ischemic Brain ◽

Chronic Dose ◽

The Brain

Abstract Background - In recent years, considerable efforts have been devoted to exploring effective therapy for cerebral ischemia. Reactive oxygen species (ROS) mediated - inflammation plays a crucial role in ischemic brain injury. Triptolide (TP) has been widely used for ischemic therapy although administrating a chronic dose of this therapy may cause serious drawbacks and higher liver toxicity. Considering these critical side effects, here we demonstrate the employment of thymoquinone (TQ) as a new alternative drug for alleviating ischemic brain damage via suppression of inflammatory cytokines by inducing Nrf2/HO-1 under a chronic dose without toxicity. Methods- We assessed a photo-thrombosis mouse model of focal cerebral ischemia to investigate the impact of the chronic dose of TQ to alleviates ischemic brain damage, meanwhile, we used Pc12 to determine the efficiency of TQ to attenuate the OGD/R induces cell death. Results- Our in vivo and in vitro results indicate that the administration of TQ drug can sufficiently mitigate the brain damage after stroke by increasing the Nrf2/HO-1 expression and thereby modulate the cell death and inflammation resulting from cerebral ischemia. The observation based on YFP mice elucidates the role of TQ therapy in recovering the brain status after injury through increasing the dendrite spines density and the ratio of YFP reporter cells with NeuN expression. Conclusions- Our study is the first to focus on the crucial role of the Nrf2/HO-1 pathway as a promising ischemic therapy under a chronic dose of TQ by increasing proliferating protein expression, decreasing inflammation and neuronal cell death as well as controlling the autophagy process.

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Role of Neuroglobin in the Neuroprotective Actions of Estradiol and Estrogenic Compounds

Cells ◽

10.3390/cells10081907 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1907

Author(s):

George E. Barreto ◽

Andrew J. McGovern ◽

Luis M. Garcia-Segura

Keyword(s):

Sex Differences ◽

Signaling Pathways ◽

Glial Cell ◽

Potential Application ◽

Neurological Diseases ◽

Brain Pathology ◽

Synthetic Steroids ◽

Neuroprotective Actions ◽

Estrogenic Regulation

Estradiol exerts neuroprotective actions that are mediated by the regulation of a variety of signaling pathways and homeostatic molecules. Among these is neuroglobin, which is upregulated by estradiol and translocated to the mitochondria to sustain neuronal and glial cell adaptation to injury. In this paper, we will discuss the role of neuroglobin in the neuroprotective mechanisms elicited by estradiol acting on neurons, astrocytes and microglia. We will also consider the role of neuroglobin in the neuroprotective actions of clinically relevant synthetic steroids, such as tibolone. Finally, the possible contribution of the estrogenic regulation of neuroglobin to the generation of sex differences in brain pathology and the potential application of neuroglobin as therapy against neurological diseases will be examined.

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Role of Oxidants in Ischemic Brain Damage

Stroke ◽

10.1161/01.str.27.6.1124 ◽

1996 ◽

Vol 27 (6) ◽

pp. 1124-1129 ◽

Cited By ~ 722

Author(s):

Pak H. Chan

Keyword(s):

Brain Damage ◽

Ischemic Brain Damage ◽

Ischemic Brain

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ROLE OF EXTRACELLULAR DOPAMINE IN HYPERGLYCEMIC EXACERBATION OF ISCHEMIC BRAIN DAMAGE IN RATS. A MICRODIALYSIS INVESTIGATION

Journal of Neurosurgical Anesthesiology ◽

10.1097/00008506-199210000-00051 ◽

1992 ◽

Vol 4 (4) ◽

pp. 316

Author(s):

W A Kofke ◽

R H Garman ◽

R L Stiller ◽

M E Rose

Keyword(s):

Brain Damage ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Extracellular Dopamine

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Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival

Cancers ◽

10.3390/cancers11040587 ◽

2019 ◽

Vol 11 (4) ◽

pp. 587 ◽

Cited By ~ 8

Author(s):

Matilda Munksgaard Thorén ◽

Katarzyna Chmielarska Masoumi ◽

Cecilia Krona ◽

Xiaoli Huang ◽

Soumi Kundu ◽

...

Keyword(s):

Cell Death ◽

Therapeutic Target ◽

Functional Role ◽

Treatment Strategies ◽

Antibody Drug Conjugate ◽

Potential Therapeutic Target ◽

Sphere Formation

New, effective treatment strategies for glioblastomas (GBMs), the most malignant and invasive brain tumors in adults, are highly needed. In this study, we investigated the potential of integrin α10β1 as a therapeutic target in GBMs. Expression levels and the role of integrin α10β1 were studied in patient-derived GBM tissues and cell lines. The effect of an antibody–drug conjugate (ADC), an integrin α10 antibody conjugated to saporin, on GBM cells and in a xenograft mouse model was studied. We found that integrin α10β1 was strongly expressed in both GBM tissues and cells, whereas morphologically unaffected brain tissues showed only minor expression. Partial or no overlap was seen with integrins α3, α6, and α7, known to be expressed in GBM. Further analysis of a subpopulation of GBM cells selected for high integrin α10 expression demonstrated increased proliferation and sphere formation. Additionally, siRNA-mediated knockdown of integrin α10 in GBM cells led to decreased migration and increased cell death. Furthermore, the ADC reduced viability and sphere formation of GBM cells and induced cell death both in vitro and in vivo. Our results demonstrate that integrin α10β1 has a functional role in GBM cells and is a novel, potential therapeutic target for the treatment of GBM.

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The role of the cyclic AMP-responsive element binding protein (CREB) in hypoxic-ischemic brain damage and repair

Molecular Brain Research ◽

10.1016/s0169-328x(96)00144-1 ◽

1996 ◽

Vol 43 (1-2) ◽

pp. 21-29 ◽

Cited By ~ 97

Author(s):

M. Walton ◽

E. Sirimanne ◽

C. Williams ◽

P. Gluckman ◽

M. Dragunow

Keyword(s):

Cyclic Amp ◽

Brain Damage ◽

Binding Protein ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Element Binding Protein ◽

Responsive Element

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Roles of NAD+, PARP-1, and Sirtuins in Cell Death, Ischemic Brain Injury, and Synchrotron Radiation X-Ray-Induced Tissue Injury

Scientifica ◽

10.1155/2013/691251 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Weihai Ying

Keyword(s):

Cell Death ◽

Brain Injury ◽

Synchrotron Radiation ◽

Brain Damage ◽

Tissue Injury ◽

Ischemic Brain Injury ◽

Biological Processes ◽

Ischemic Brain ◽

X Ray ◽

Parp 1

NAD+plays crucial roles in a variety of biological processes including energy metabolism, aging, and calcium homeostasis. Multiple studies have also shown that NAD+administration can profoundly decrease oxidative cell death and ischemic brain injury. A number of recent studies have further indicated that NAD+administration can decrease ischemic brain damage, traumatic brain damage and synchrotron radiation X-ray-induced tissue injury by such mechanisms as inhibiting inflammation, decreasing autophagy, and reducing DNA damage. Our latest study that applies nano-particles as a NAD+carrier has also provided first direct evidence demonstrating a key role of NAD+depletion in oxidative stress-induced ATP depletion. Poly(ADP-ribose) polymerase-1 (PARP-1) and sirtuins are key NAD+-consuming enzymes that mediate multiple biological processes. Recent studies have provided new information regarding PARP-1 and sirtuins in cell death, ischemic brain damage and synchrotron radiation X-ray-induced tissue damage. These findings have collectively supported the hypothesis that NAD+metabolism, PARP-1 and sirtuins play fundamental roles in oxidative stress-induced cell death, ischemic brain injury, and radiation injury. The findings have also supported “the Central Regulatory Network Hypothesis”, which proposes that a fundamental network that consists of ATP, NAD+and Ca2+as its key components is the essential network regulating various biological processes.

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