Essential Role of Cytoplasmic cdk5 and Prx2 in Multiple Ischemic Injury Models,<i>In Vivo</i>

Rashidian, Juliet; Rousseaux, Maxime W.C.; Venderová, Kateřina; Qu, Dianbo; Callaghan, Steve; Phillips, Maryam; Bland, Ross; During, Matthew J.; Mao, Zixu; Slack, Ruth S.; Park, David

doi:10.1523/jneurosci.3892-09.2009

Cited by 70 publications

(35 citation statements)

References 35 publications

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“…In various brain tissue injuries, the increased expression of Prx proteins within brain cells has been observed and considered to diminish ROS (Patenaude et al 2005). Consistent with this hypothesis, such an intracellular expression of Prx proteins has been reported to play a neuroprotective role (Rashidian et al 2009). These results indicate that Prx family members are strongly induced inside the injured ischemic cells to improve their survival.…”

Section: Damps In Ischemic Brain Tissuementioning

confidence: 72%

Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke

Shichita

Ago

Kamouchi

et al. 2012

Journal of Neurochemistry

129

102

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Post-ischemic inflammation is an essential step in the progression of ischemic stroke. This review focuses on the function of infiltrating immune cells, macrophages, and T cells, in ischemic brain injury. The brain is a sterile organ; however, the activation of Toll-like receptor (TLR) 2 and TLR4 is pivotal in the beginning of post-ischemic inflammation. Some endogenous TLR ligands are released from injured brain cells, including high mobility group box 1 and peroxiredoxin family proteins, and activate the infiltrating macrophages and induce the expression of inflammatory cytokines. Following this step, T cells also infiltrate into the ischemic brain and mediate postischemic inflammation in the delayed phase. Various cytokines from helper T cells and cdT cells function as neurotoxic (IL-23/IL-17, IFN-c) or neuroprotective (IL-10, IL-4) mediators. Novel neuroprotective strategies should therefore be developed through more detailed understanding of this process and the regulation of post-ischemic inflammation. Keywords: cytokine, DAMPs, macrophage, T cell, TLR. J. Neurochem. Stroke is a leading cause of death and disability worldwide, and approximately, 70-80% of all cases are ischemic stroke. The only globally approved treatment for ischemic stroke is the intravenous administration of alteplase [tissue plasminogen activator (tPA)], which is a time-dependent therapy that must be provided within 4.5 h after the stroke onset. Thus, the beneficial effect of tPA is limited to a small proportion of stroke patients. There is a need for an efficacious therapy that can be administered beyond this time window (Lo 2010;Moskowitz et al. 2010).Post-ischemic inflammation is an essential step in ischemic brain injury (Eltzschig and Eckle 2011;Iadecola and Anrather 2011). The primary (acute) and secondary (delayed) progression of the infarct lesion are directly linked to the prognosis of ischemic stroke patients. The deprivation of oxygen, glucose, and other nutrients caused by the insufficient blood supply results in the dysfunction of cerebrovascular units, which consist of glial cells, endothelial cells, Received May 31, 2012; revised manuscript received July 9, 2012; accepted July 20, 2012. Address correspondence and reprint requests to Hiroaki Ooboshi, Department of Internal Medicine, Fukuoka Dental College Medical and Dental Hospital, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan. E-mail: ooboshi@college.fdcnet.ac.jp Abbreviations used: BBB, blood-brain barrier; BM, bone marrow; DAMPs, danger-associated molecular patterns; HMGB1, high mobility group box 1; ICAM-1, intercellular adhesion molecule-1; MMPs, matrix metalloproteinases; NKT, natural killer T; Prx, peroxiredoxin; ROS, reactive oxygen species; S1P, Sphingosine-1-phosphate; TCR, T-cell receptor; TLRs, Toll-like receptors; TNF, Tumor necrosis factor; tPA, tissue plasminogen activator. pericytes, and neurons (del Zoppo 2006;Iadecola 2004;Kamouchi et al. 2011). Brain cells fail to maintain the neuronal microenvironment, leading to blood-brain barrier (B...

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Section: Damps In Ischemic Brain Tissuementioning

confidence: 72%

Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke

Shichita

Ago

Kamouchi

et al. 2012

Journal of Neurochemistry

129

102

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“…HARDINGHAM AND LIPTON kinase 5 (cdk5) (23). One could envisage that inactivation of Prxs makes it harder for the brain to cope with elevated ROS and RNS generation after stroke and possibly other neurodegenerative disorders.…”

mentioning

confidence: 99%

Regulation of Neuronal Oxidative and Nitrosative Stress by Endogenous Protective Pathways and Disease Processes

Hardingham

Lipton

2011

Antioxidants & Redox Signaling

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Oxidative/nitrosative stress contributes to the etiology of many neurological disorders in the developing and aged/mature central nervous system, including acute trauma such as ischemia and hyperoxia, as well as chronic diseases such as Alzheimer's and Parkinson's diseases. In addition to the accumulation of nonspecific oxidative damage, it is becoming clear that pathological conditions lead to the oxidative/nitrosative modification of specific proteins, including those involved in apoptosis, proteolysis, and protein (mis)folding. Several disorders, including stroke and Parkinson's disease, are associated with inactivating modifications of antioxidant enzymes themselves, thus compromising antioxidant defenses. Conversely, neuroprotective pathways, such as neurotrophin- and synaptic activity-induced signals, can upregulate key antioxidant systems, potentially contributing to the cytoprotective actions of adaptive stress responses following exercise or calorie-restriction. On the flip-side, hypofunction of these pathways is associated with the death of developing neurons. An increased knowledge of how neuronal antioxidant systems are controlled in health and disease is unearthing therapeutic targets in several disorders. Moreover, the emerging importance of master regulators of antioxidant defenses such as nuclear factor-erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) is revealing ways through which intrinsic defenses may be manipulated to combat oxidative/nitrosative stress. Such approaches offer an alternative strategy to classical antioxidant interventions based on the administration of free radical scavengers and spin-traps.

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“…There are reports that Cdk5 activity is upregulated in human stroke calpain upregulation and hyper activation of Cdk5/p25 have been identified in animal models of ischemia and may be responsible for downstream pathologies associated with neuronal death [63][64][65]. Accordingly, hyper activated Cdk5/p25 has been suggested as a target for therapeutic intervention after a stroke [66].…”

Section: Brain Ischemia; Cdk5 Activation and Regulation By P5 Peptidesmentioning

confidence: 99%

Peptides Derived from Neuronal Cell Cycle like Kinase 5 Activator p35, in Neurodegeneration; Pathology and Therapy

Grant¹,

Bhaskar²,

Binukumar³

et al. 2017

J Alzheimers Dis Parkinsonism

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Essential Role of Cytoplasmic cdk5 and Prx2 in Multiple Ischemic Injury Models,In Vivo

Cited by 70 publications

References 35 publications

Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke

Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke

Regulation of Neuronal Oxidative and Nitrosative Stress by Endogenous Protective Pathways and Disease Processes

Peptides Derived from Neuronal Cell Cycle like Kinase 5 Activator p35, in Neurodegeneration; Pathology and Therapy

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