针对痴呆和认知障碍的肝脏靶点：膳食宏量营养素和糖尿病治疗学。
Targeting the liver in dementia and cognitive impairment: Dietary macronutrients and diabetic therapeutics.
机构信息
Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2008, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW 2008, Australia; Sydney Nano Institute, The University of Sydney, Sydney, NSW 2008, Australia; ANZAC Research Institute & Centre for Education and Research on Ageing, Concord Repatriation General Hospital, Concord, NSW 2139, Australia.
Department of Health and Exercise Science & Centre for Healthy Aging, Colorado State University, CO 80523, United States.
出版信息
Adv Drug Deliv Rev. 2022 Nov;190:114537. doi: 10.1016/j.addr.2022.114537. Epub 2022 Sep 14.
Many people living with dementia and cognitive impairment have dysfunctional mitochondrial and insulin-glucose metabolism resembling type 2 diabetes mellitus and old age. Evidence from human trials shows that nutritional interventions and anti-diabetic medicines that target nutrient-sensing pathways overcome these deficits in glucose and energy metabolism and can improve cognition and/or reduce symptoms of dementia. The liver is the main organ that mediates the systemic effects of diets and many diabetic medicines; therefore, it is an intermediate target for such dementia interventions. A challenge is the efficacy of these treatments in older age. Solutions include the targeted hepatic delivery of diabetic medicines using nanotechnologies and titration of macronutrients to optimize hepatic energy metabolism.
许多患有痴呆症和认知障碍的人存在功能失调的线粒体和胰岛素-葡萄糖代谢，类似于 2 型糖尿病和老年。来自人体试验的证据表明，营养干预和针对营养感应途径的抗糖尿病药物可以克服葡萄糖和能量代谢的这些缺陷，并改善认知能力和/或减轻痴呆症状。肝脏是介导饮食和许多糖尿病药物全身作用的主要器官；因此，它是此类痴呆症干预的中间目标。一个挑战是这些治疗方法在老年时的疗效。解决方案包括使用纳米技术靶向肝脏递送糖尿病药物以及调整宏量营养素以优化肝脏能量代谢。
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