Novel GLP-1R/GIPR co-agonist “twincretin” is neuroprotective in cell and rodent models of mild traumatic brain injury

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• 作者：Ian A. Tamargo^a ; ^{iatamargo@gmail.com} ; Miaad Bader^b ; Yazhou Li^a ; Seong-Jin Yu^c ; Yun Wang^c ; Konrad Talbot^d ; Richard D. DiMarchi^e ; Chaim G. Pick^b ; ^f ; Nigel H. Greig^a ; ^{Greign@mail.nih.gov}
• 关键词：BCA ; bicinchoninic acid ; cAMP ; cyclic AMP ; CDC ; Centers for Disease Control and Prevention ; CREB ; cyclic AMP response element-binding protein ; Ex-4 ; exendin-4 ; Ex 9&ndash ; 39 ; exendin fragment 9&ndash ; 39 ; GIP ; glucose-dependent insulinotropic peptide ; GIPR ; glucose-dependent insulinotropic peptide receptor ; GLP-1 ; glucagon-like peptide-1 ; GLP-1R ; glucagon-like peptide-1 receptor ; H2O2 ; hydrogen peroxide ; LDH ; lactate dehydrogenase ; mTBI ; mild traumatic brain injury ; MTS ; 3-(4 ; 5-dimethylthiazol-2-
• 刊名：Experimental Neurology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：288
• 期：Complete
• 页码：176-186
• 全文大小：1221 K
• 卷排序：288

文摘

The dual GLP-1/GIP receptor agonist “twincretin” was evaluated for neurotrophic and neuroprotective actions in cell and in vivo models of mild TBI. Twincretin provided neurotrophic properties in immortal human SH-SY5Y neuronal cells - elevating cAMP levels and pCREB. Twincretin provided neuroprotection against oxidative stress and glutamate excitotoxicity in human SH-SY5Y cells. Twincretin protected rat primary cultures of dopaminergic ventral mesencephalon neurons from 6-hydroxydopamine-induced injury. A clinically translatable dose of twincretin fully mitigated mild TBI-induced spatial and visual memory deficits in a mouse close head injury model. Twincretin mediated mitigation of cellular and in vivo TBI-induced impairments highlight the agent for evaluation in neurodegenerative disorders.