The open drug discovery journal最新文献_第2页

Neuroprotective Drugs in Traumatic CNS Injury. 创伤性中枢神经系统损伤中的神经保护药物。

The open drug discovery journal Pub Date : 2010-01-01

Supriti Samantaray, Nakul P Thakore, Denise D Matzelle, Abhay Varma, Swapan K Ray, Naren L Banik

引用次数: 0

Estrogen and P2 Purinergic Receptor Systems in Microglia: Therapeutic Targets for Neuroprotection. 小胶质细胞中的雌激素和P2嘌呤能受体系统：神经保护的治疗靶点。

The open drug discovery journal Pub Date : 2010-01-01 DOI: 10.2174/1877381801002010148

Jessica M Crain, Jyoti J Watters

{"title":"Estrogen and P2 Purinergic Receptor Systems in Microglia: Therapeutic Targets for Neuroprotection.","authors":"Jessica M Crain, Jyoti J Watters","doi":"10.2174/1877381801002010148","DOIUrl":"10.2174/1877381801002010148","url":null,"abstract":"Microglia, the primary resident immune cell population in the CNS, react to signals of injury or infection and produce inflammatory cytokines, chemokines, and reactive oxygen species, many of which can be neurotoxic in large quantities. Indeed microglial hyperactivation is thought to contribute to the pathology of many neurodegenerative disorders as well as ischemic and traumatic brain injuries, suggesting that agents with the capacity to target microglial activities may be beneficial for treating neuronal injury. In this review, we discuss two seemingly unrelated microglial receptor signaling systems that potently modulate many microglial properties; purinergic P2 and estrogen receptors. Purinergic receptors regulate key microglial functions, including their production of pro-inflammatory cytokines, neurotrophic factors, migration, phagocytosis and chemotaxis. Many of these same endpoints are also altered by estrogen receptor signaling in microglia. Here we summarize the current microglial research in both receptor areas, particularly as it relates to ischemic and traumatic CNS injuries. We provide evidence from our own laboratory of potential cross-talk between these receptor systems and discuss evidence indicating that both purinergic and estrogen receptors may represent useful therapeutic targets for the treatment of CNS disorders.","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 ","pages":"148-167"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180920/pdf/nihms263927.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30032176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erythropoietin protects against acute kidney injury and failure 促红细胞生成素可以防止急性肾损伤和衰竭

The open drug discovery journal Pub Date : 2010-01-01 DOI: 10.2174/1877381801002010008

David W. Johnson, D. Vesey, G. Gobe

{"title":"Erythropoietin protects against acute kidney injury and failure","authors":"David W. Johnson, D. Vesey, G. Gobe","doi":"10.2174/1877381801002010008","DOIUrl":"https://doi.org/10.2174/1877381801002010008","url":null,"abstract":"Erythropoietin (EPO) has traditionally been viewed as a hormone dedicated to the regulation of erythropoiesis. More recently, the EPO receptor (EPOR) has been found to be expressed in a large variety of non-haematopoietic tissues suggesting that EPO might have important actions beyond erythrocyte production. Over the last five years, short-term, high dose administration of EPO has been shown to ameliorate acute kidney injury (AKI), as evidenced by suppressed tubular epithelial apoptosis, enhanced tubular epithelial proliferation, and hastened functional recovery. This renoprotective effect is still apparent when administration is delayed up to 6 hours after the onset of injury and has been demonstrated in a variety of animals (mouse, rat, dog, pig) in response to a variety of renal insults (ischaemia-reperfusion injury, cisplatin, ureteral obstruction, cyclosporine, radiographic contrast, endotoxaemia, heat-shock, and aristolochic acid). Based on these highly encouraging results, several large randomised controlled trials of EPO therapy in ischaemic or toxic AKI are currently underway. The purpose of this article is to review the experimental and clinical evidence for a renoprotective benefit of EPO in acute kidney injury (AKI), the potential mechanisms underpinning these renoprotective actions and possible future directions for research in this important area.","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 1","pages":"8-17"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68151622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Targeting Dopamine in Acute Traumatic Brain Injury. 急性创伤性脑损伤靶向多巴胺的研究。

The open drug discovery journal Pub Date : 2010-01-01 DOI: 10.2174/1877381801002010119

James W Bales, Anthony E Kline, Amy K Wagner, C Edward Dixon

{"title":"Targeting Dopamine in Acute Traumatic Brain Injury.","authors":"James W Bales, Anthony E Kline, Amy K Wagner, C Edward Dixon","doi":"10.2174/1877381801002010119","DOIUrl":"10.2174/1877381801002010119","url":null,"abstract":"In addition to the initial mechanical damage, traumatic brain injury (TBI) induces a series of secondary insults, such as, but not limited to, excitotoxicity, metabolic disruption, and oxidative stress. Neuroprotective strategies after TBI have traditionally focused on cellular preservation as the measurable endpoint although multiple lines of evidence indicate that even with significant neuronal sparing deficits remain at both the cellular and behavioral level. As such, the development of therapies that can effectively confer both neuronal sparing and post-injury functional benefit is critical to providing the best treatment options for clinical TBI. Targeting dopaminergic signaling pathways is a novel approach in TBI that provides benefits to both neuronal survival and functional outcomes. Dopamine, like glutamate, can cause oxidative stress and significant cellular dysfunction when either depleted or over-expressed, and also plays an important role in central nervous system inflammation. The purpose of this review is to discuss dopamine in acute TBI and the role that dopaminergic therapies have as neuroprotective strategies.","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 ","pages":"119-128"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269831/pdf/nihms-259600.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30438444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adenosine kinase is a new therapeutic target to prevent ischemic neuronal death. 腺苷激酶是预防缺血性神经元死亡的新靶点。

The open drug discovery journal Pub Date : 2010-01-01

Detlev Boison, Hai-Ying Shen

{"title":"Adenosine kinase is a new therapeutic target to prevent ischemic neuronal death.","authors":"Detlev Boison, Hai-Ying Shen","doi":"","DOIUrl":"","url":null,"abstract":"The brain has evolved several endogenous mechanisms to protect itself from the deleterious consequences of stroke. One of those endogenous neuroprotective systems is centered on the purine ribonucleoside adenosine, which exerts potent neuroprotective functions within the brain. One major goal in therapeutic stroke research is to explore and utilize such endogenous neuroprotective mechanisms therapeutically. This review illustrates molecular approaches to study the role of the adenosine system within the context of stroke and highlights innovative therapeutic approaches aimed at increasing adenosinergic function. New research data suggest that the major adenosine regulating enzyme adenosine kinase (ADK) plays a prominent role in determining the brain's susceptibility to ischemic injury. Thus, endogenous ADK is rapidly downregulated following a stroke, possibly an endogenous neuroprotective mechanism aimed at raising ambient levels of adenosine in brain. Conversely, transgenic overexpression of ADK in brain renders the brain more susceptible to stroke-induced neuronal cell loss. In the present review we will first summarize the physiological role of adenosine metabolism within the context of ischemic brain injury. Next, we will highlight the key role of ADK in determining the brain's susceptibility to ischemic injury, and finally we will discuss potential therapeutic applications of adenosine augmentation to provide neuroprotection in stroke.","PeriodicalId":89503,"journal":{"name":"The open drug discovery journal","volume":"2 3","pages":"108-118"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3786597/pdf/nihms213853.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31777690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular Ion Channel Inhibitor Antibodies 细胞外离子通道抑制剂抗体

The open drug discovery journal Pub Date : 2009-10-27 DOI: 10.2174/1877381800901010036

Jacqueline Naylor, D. Beech

引用次数: 20

Setbacks in the Clinical Development of TRPV1 Antagonists: What Next? TRPV1拮抗剂临床开发的挫折:下一步是什么?

The open drug discovery journal Pub Date : 2009-03-03 DOI: 10.2174/1877381800901010001

N. Gavva

引用次数: 13