Attenuation of Inflammation by DJ-1 May Be a Drug Target for Cerebral Ischemia–Reperfusion Injury

Zhao, Na; Wang, Tingting; Li, Peng; Li, Yumei; Zhao, Yong; Yu, Shanshan

doi:10.1007/s11064-021-03288-z

Cited by 8 publications

(5 citation statements)

References 38 publications

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“…52 In addition, overexpression of DJ-1 or Nln through AAV gene therapy can also reduce stroke volume to varying degrees, inhibit pro-inflammatory cytokines, promote the expression of anti-inflammatory factors, and alleviate stroke injury. 53,54 For this purpose, Mätlik K et al…”

Section: Ta B L E 1 (Continued)mentioning

confidence: 99%

“…[110][111][112] In stroke research, ubiquitous promoters such as the non-specific cytomegalovirus (CMV) or chickenβ-actin hybrid (CAG) are expressed in most CNS cells, primarily neurons and some scattered astrocytes. 79,103,113 Various promoters can drive specific transgene expressions, such as the hSyn promoter driving neuron-specific gene expression, 53,75,76,106,114 the GFAP promoter driving astrocyte-specific expression, 44,66,73,88 the F4/80 promoter driving microglia-specific expression, 44,66,73 the CaMK2a promoter driving glutamatergic neuronal expression, 80 and the Olig2 promoter driving oligodendrocyte-specific expression. 115 Additionally, regulatory elements such as the Tie1 promoter can drive brain endothelial cell-specific expression 57,116 and the HIF-1α…”

Section: Promotersmentioning

confidence: 99%

“…The overexpression of serine proteinase inhibitor A3N (serpinA3N) significantly reduced the size of cerebral infarcts in tMCAO mice 24 h after surgery and indirectly inhibited neuroinflammation 52 . In addition, overexpression of DJ‐1 or Nln through AAV gene therapy can also reduce stroke volume to varying degrees, inhibit pro‐inflammatory cytokines, promote the expression of anti‐inflammatory factors, and alleviate stroke injury 53,54 . For this purpose, Mätlik K et al injected AAV7‐mediated mesencephalic astrocyte‐derived neurotrophic factor (AAV7‐MANF) into the peri‐infarcted area of rats 2 days after distal middle cerebral artery occlusion surgery, which resulted in an increased number of phagocytic immune cells in the subcortical area 4 days post‐surgery with enhanced behavioral recovery 55 .…”

Section: Therapeutic Potential Of Aav Vectors In Preclinical Stroke M...mentioning

confidence: 99%

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Gene therapy of adeno‐associated virus (AAV) vectors in preclinical models of ischemic stroke

et al. 2023

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Stroke has been associated with devastating clinical outcomes, with current treatment strategies proving largely ineffective. Therefore, there is a need to explore alternative treatment options for addressing post‐stroke functional deficits. Gene therapy utilizing adeno‐associated viruses (AAVs) as a critical gene vector delivering genes to the central nervous system (CNS) gene delivery has emerged as a promising approach for treating various CNS diseases. This review aims to provide an overview of the biological characteristics of AAV vectors and the therapeutic advancements observed in preclinical models of ischemic stroke. The study further investigates the potential of manipulating AAV vectors in preclinical applications, emphasizing the challenges and prospects in the selection of viral vectors, drug delivery strategies, immune reactions, and clinical translation.

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Section: Ta B L E 1 (Continued)mentioning

confidence: 99%

Section: Promotersmentioning

confidence: 99%

Section: Therapeutic Potential Of Aav Vectors In Preclinical Stroke M...mentioning

confidence: 99%

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Gene therapy of adeno‐associated virus (AAV) vectors in preclinical models of ischemic stroke

et al. 2023

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“…Indeed, in vivo analyses have indicated that the absence or downregulation of DJ-1 increased the sensitivity to ischemia and enhanced the infarct size in the brain [22,[87][88][89][90] and heart [91,92]. In contrast, DJ-1 upregulation has been described to rescue post-ischemic cerebral [87,89,90,93,94] and myocardial damage [95][96][97]. The principal protective mechanism promoted by DJ-1 against ischemia seems to be related to the stabilization of HIF-1α (Figure 2).…”

Section: Dj-1 Involvement In Hypoxia Response: Implications For Alsmentioning

confidence: 99%

Molecular and Physiological Determinants of Amyotrophic Lateral Sclerosis: What the DJ-1 Protein Teaches Us

Sandrelli

Bisaglia

2023

IJMS

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Amyotrophic lateral sclerosis (ALS) is an adult-onset disease which causes the progressive degeneration of cortical and spinal motoneurons, leading to death a few years after the first symptom onset. ALS is mainly a sporadic disorder, and its causative mechanisms are mostly unclear. About 5–10% of cases have a genetic inheritance, and the study of ALS-associated genes has been fundamental in defining the pathological pathways likely also involved in the sporadic forms of the disease. Mutations affecting the DJ-1 gene appear to explain a subset of familial ALS forms. DJ-1 is involved in multiple molecular mechanisms, acting primarily as a protective agent against oxidative stress. Here, we focus on the involvement of DJ-1 in interconnected cellular functions related to mitochondrial homeostasis, reactive oxygen species (ROS) levels, energy metabolism, and hypoxia response, in both physiological and pathological conditions. We discuss the possibility that impairments in one of these pathways may affect the others, contributing to a pathological background in which additional environmental or genetic factors may act in favor of the onset and/or progression of ALS. These pathways may represent potential therapeutic targets to reduce the likelihood of developing ALS and/or slow disease progression.

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“…Copyright © 2022 the authors ischemic-induced DJ-1 translocation into the healthy mitochondria and further extracellular secretion ensure endogenous neuroprotection in primary rat neural cells (Kaneko et al, 2014). A recent study reported that overexpression of DJ-1 can alleviate pathological brain injury and regulate inflammatory cytokines during I/R injury (Zhao et al, 2021). In an MCAO/R mouse model, adeno-associated viruses-induced DJ-1 upregulation improved neurological function by increasing the anti-inflammatory cytokines IL-10 and IL-4 expression and reducing the proinflammatory cytokines IL-1β and TNF-α levels.…”

Section: Cerebral Ischemia-reperfusion (I/r) Injurymentioning

confidence: 99%

Redox-sensitive DJ-1 protein: an insight into physiological roles, secretion, and therapeutic target

Dash

Urano

Saito

et al. 2022

Redox Experimental Medicine

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The highly conserved DJ-1 protein fundamentally acts as a redox sensor conferring antioxidative cytoprotection under oxidative insults. DJ-1 preferentially undergoes oxidation at 106 cysteine residue (Cys106) under oxidative stress. Although initially identified as an oncogene, emerging evidence suggests the essential roles of DJ-1 in modulating numerous physiological processes involved in cellular growth, development, survival, and death. Compromised DJ-1 expression and function directly or indirectly trigger signaling cascades leading to pathophysiological conditions including neurodegeneration, cancer, stroke, and inflammatory diseases. Besides the intracellular functions, enhanced DJ-1 secretion into the extracellular fluid, including cerebrospinal fluid and blood, is related to Parkinson’s disease (PD) and cancer pathogenesis. Here we review the current knowledge regarding DJ-1’s roles as a ubiquitous cytoprotective protein controlling numerous signaling pathways, secretion, and therapeutic potentials.

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Attenuation of Inflammation by DJ-1 May Be a Drug Target for Cerebral Ischemia–Reperfusion Injury

Cited by 8 publications

References 38 publications

Gene therapy of adeno‐associated virus (AAV) vectors in preclinical models of ischemic stroke

Gene therapy of adeno‐associated virus (AAV) vectors in preclinical models of ischemic stroke

Molecular and Physiological Determinants of Amyotrophic Lateral Sclerosis: What the DJ-1 Protein Teaches Us

Redox-sensitive DJ-1 protein: an insight into physiological roles, secretion, and therapeutic target

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