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- Peter S. Vosler
- From the Department of Neurology (P.S.V., S.H.G., L.R.W., J.C.), University of Pittsburgh School of Medicine, Pa; State Key Laboratory of Medical Neurobiology (J.C.), Fudan University School of Medicine, Shanghai, China; and the Geriatric Research, Educational, and Clinical Center (S.H.G., J.C.), Veterans Affairs Pittsburgh Health Care System, Pa.
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- Steven H. Graham
- From the Department of Neurology (P.S.V., S.H.G., L.R.W., J.C.), University of Pittsburgh School of Medicine, Pa; State Key Laboratory of Medical Neurobiology (J.C.), Fudan University School of Medicine, Shanghai, China; and the Geriatric Research, Educational, and Clinical Center (S.H.G., J.C.), Veterans Affairs Pittsburgh Health Care System, Pa.
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- Lawrence R. Wechsler
- From the Department of Neurology (P.S.V., S.H.G., L.R.W., J.C.), University of Pittsburgh School of Medicine, Pa; State Key Laboratory of Medical Neurobiology (J.C.), Fudan University School of Medicine, Shanghai, China; and the Geriatric Research, Educational, and Clinical Center (S.H.G., J.C.), Veterans Affairs Pittsburgh Health Care System, Pa.
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- Jun Chen
- From the Department of Neurology (P.S.V., S.H.G., L.R.W., J.C.), University of Pittsburgh School of Medicine, Pa; State Key Laboratory of Medical Neurobiology (J.C.), Fudan University School of Medicine, Shanghai, China; and the Geriatric Research, Educational, and Clinical Center (S.H.G., J.C.), Veterans Affairs Pittsburgh Health Care System, Pa.
書誌事項
- タイトル別名
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- Focusing Basic Science Research Toward Development of Clinically Translatable Therapeutics
説明
<jats:p> <jats:bold> <jats:italic>Background and Purpose—</jats:italic> </jats:bold> Stroke is a major cause of death and disability, and it is imperative to develop therapeutics to mitigate stroke-related injury. Despite many promising prospects, attempts at translating neuroprotective agents that show success in animal models of stroke have resulted in very limited clinical success. </jats:p> <jats:p> <jats:bold> <jats:italic>Summary of Review—</jats:italic> </jats:bold> This review discusses reasons for the lack of translational success based on the therapeutic targets tested and the pathophysiology of stroke. New recanalization therapies and alternative therapeutic strategies are discussed concerning mitochondria-mediated cell death. Mitochondrial death-regulation pathways are divided into 3 categories: Upstream signaling pathways, agents that target mitochondria directly, and downstream death-execution effectors. The apoptosis signal-related kinase/c-Jun-terminal kinase pathway is used as an example to provide rationale as to why inhibiting signaling pathway upstream of mitochondrial dysfunction is a promising therapeutic approach. Finally, the mechanisms of autophagy and mitochondrial biogenesis are discussed in relation to stroke. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> Increasing evidence suggests that reperfusion is necessary for improved neurological outcomes after stroke. Development of improved recanalization methods with increased therapeutic windows will aid in improving clinical outcome. Adjunct neuroprotective interventions must also be developed to ensure maximal brain tissue salvage. Targeting prodeath signaling pathways upstream of mitochondrial damage is promising for potential clinically effective treatment. Further understanding of the roles of equilibrium of autophagy and mitochondrial biogenesis in the pathogenesis of stroke could also lead to novel therapeutics. </jats:p>
収録刊行物
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- Stroke
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Stroke 40 (9), 3149-3155, 2009-09
Ovid Technologies (Wolters Kluwer Health)