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Insulin mediated novel therapies for the treatment of Alzheimer's disease
Life Sciences ( IF 5.2 ) Pub Date : 2020-03-10 , DOI: 10.1016/j.lfs.2020.117540 Sunil Kumar Dubey 1 , K K Lakshmi 1 , Kowthavarapu Venkata Krishna 1 , Mukta Agrawal 2 , Gautam Singhvi 1 , Ranendra Narayana Saha 3 , Swarnlata Saraf 4 , Shailendra Saraf 4 , Rahul Shukla 5 , Amit Alexander 6
Life Sciences ( IF 5.2 ) Pub Date : 2020-03-10 , DOI: 10.1016/j.lfs.2020.117540 Sunil Kumar Dubey 1 , K K Lakshmi 1 , Kowthavarapu Venkata Krishna 1 , Mukta Agrawal 2 , Gautam Singhvi 1 , Ranendra Narayana Saha 3 , Swarnlata Saraf 4 , Shailendra Saraf 4 , Rahul Shukla 5 , Amit Alexander 6
Affiliation
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Alzheimer's disease, a progressive neurodegenerative disorder, is one of the leading causes of death in the USA, along with cancer and cardiac disorders. AD is characterized by various neurological factors like amyloid plaques, tau hyperphosphorylation, mitochondrial dysfunction, acetylcholine deficiency, etc. Together, impaired insulin signaling in the brain is also observed as essential factor to be considered in AD pathophysiology. Hence, currently researchers focused on studying the effect of brain insulin metabolism and relation of diabetes with AD. Based on the investigations, AD is also considered as type 3 or brain diabetes. Besides the traditional view of correlating AD with aging, a better understanding of various pathological factors and effects of other physical ailments is necessary to develop a promising therapeutic approach. There is a vast scope of studying the relation of systemic insulin level, insulin signaling, its neuroprotective potency and effect of diabetes on AD progression. The present work describes worldwide status of AD and its relation with diabetes mellitus and insulin metabolism; pathophysiology of AD; different metabolic pathways associating insulin metabolism with AD; insulin receptor and signaling in the brain; glucose metabolism; insulin resistance; and various preclinical and clinical studies reported insulin-based therapies to treat AD via systemic route and through direct intranasal delivery to the brain.
中文翻译：
胰岛素介导的治疗阿尔茨海默病的新疗法
阿尔茨海默病是一种进行性神经退行性疾病，与癌症和心脏病一样，是美国的主要原因之一。 AD 的特征是各种神经系统因素，如淀粉样斑块、tau 蛋白过度磷酸化、线粒体功能障碍、乙酰胆碱缺乏等。此外，大脑中胰岛素信号传导受损也被认为是 AD 病理生理学中需要考虑的重要因素。因此，目前研究人员重点研究脑胰岛素代谢的影响以及糖尿病与AD的关系。根据调查，AD 也被认为是 3 型或脑部糖尿病。除了将 AD 与衰老相关的传统观点之外，更好地了解各种病理因素和其他身体疾病的影响对于开发有前途的治疗方法也是必要的。人们对全身胰岛素水平、胰岛素信号传导、其神经保护效力以及糖尿病对 AD 进展的影响之间的关系进行了广泛的研究。目前的工作描述了 AD 的全球状况及其与糖尿病和胰岛素代谢的关系； AD 的病理生理学；胰岛素代谢与 AD 相关的不同代谢途径；大脑中的胰岛素受体和信号传导；葡萄糖代谢；胰岛素抵抗;各种临床前和临床研究报告了基于胰岛素的疗法通过全身途径和直接鼻内递送至大脑来治疗 AD。
更新日期：2020-03-10
中文翻译：
胰岛素介导的治疗阿尔茨海默病的新疗法
阿尔茨海默病是一种进行性神经退行性疾病，与癌症和心脏病一样，是美国的主要原因之一。 AD 的特征是各种神经系统因素，如淀粉样斑块、tau 蛋白过度磷酸化、线粒体功能障碍、乙酰胆碱缺乏等。此外，大脑中胰岛素信号传导受损也被认为是 AD 病理生理学中需要考虑的重要因素。因此，目前研究人员重点研究脑胰岛素代谢的影响以及糖尿病与AD的关系。根据调查，AD 也被认为是 3 型或脑部糖尿病。除了将 AD 与衰老相关的传统观点之外，更好地了解各种病理因素和其他身体疾病的影响对于开发有前途的治疗方法也是必要的。人们对全身胰岛素水平、胰岛素信号传导、其神经保护效力以及糖尿病对 AD 进展的影响之间的关系进行了广泛的研究。目前的工作描述了 AD 的全球状况及其与糖尿病和胰岛素代谢的关系； AD 的病理生理学；胰岛素代谢与 AD 相关的不同代谢途径；大脑中的胰岛素受体和信号传导；葡萄糖代谢；胰岛素抵抗;各种临床前和临床研究报告了基于胰岛素的疗法通过全身途径和直接鼻内递送至大脑来治疗 AD。
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