CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal.
Antioxid Redox Signal. 2021 Mar 10;34(8):631-649. doi: 10.1089/ars.2020.8056. Epub 2020 Apr 20.
It is of common sense that the world population is aging and life expectancy is increasing. However, as the population ages, there is also an exponential risk to live into the ages where the brain-related frailties and neurodegenerative diseases develop. Hand in hand with those events, the world is witnessing a major upsurge in diabetes diagnostics. Remarkably, all of this seems to be narrowly related, and clinical and research communities highlight for the upcoming threat that it will represent for the present and future generations. It is of utmost importance to clarify the influence of diabetes-related metabolic features on brain health and the mechanisms underlying the increased likelihood of developing neurodegenerative diseases, in particular Alzheimer's disease. Thereupon, a wealth of evidence suggests that mitochondria and associated oxidative stress are at the root of the link between diabetes and co-occurring disorders in the brain. The scientific community has been challenged with constant failures of clinical trials raising major issues in the advance of the therapeutic field to fight chronic diseases epidemics. Thus, a change of paradigms is urgently needed. It has become urgent to identify new and solid candidates able to clinically reproduce the positive outcomes obtained in preclinical studies. On this basis, strategies settled to counteract diabetes-induced neurodegeneration encompassing mitochondrial dysfunction, redox status imbalance, and/or insulin dysregulation seem worth to follow. Hopefully, ongoing innovative research based on reliable experimental tools will soon bring the desired answers allowing pharmaceutical industry to apply such knowledge to human medicine.
人口老龄化和预期寿命延长是常识。然而,随着人口老龄化,人们进入大脑相关脆弱性和神经退行性疾病发展阶段的风险呈指数级增长。与此同时,世界上糖尿病诊断也在大幅增加。值得注意的是,所有这些似乎都密切相关,临床和研究界都强调了这将对当前和未来几代人构成的威胁。阐明糖尿病相关代谢特征对大脑健康的影响以及导致神经退行性疾病(特别是阿尔茨海默病)发生几率增加的机制至关重要。大量证据表明,线粒体和相关氧化应激是糖尿病与大脑中同时发生的疾病之间联系的根源。科学界一直面临临床试验屡屡失败的挑战,这给治疗领域应对慢性疾病流行的进展带来了重大问题。因此,迫切需要改变范式。迫切需要确定新的可靠候选药物,这些药物能够在临床上复制临床前研究中获得的积极结果。在此基础上,针对糖尿病引起的神经退行性变的策略,包括线粒体功能障碍、氧化还原状态失衡和/或胰岛素失调,似乎值得关注。希望基于可靠实验工具的持续创新研究将很快带来所需的答案,使制药行业能够将这些知识应用于人类医学。