Howard Hughes Medical Institute, Glenn Center for Ageing Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies , 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Philos Trans R Soc Lond B Biol Sci. 2011 Jan 12;366(1561):94-8. doi: 10.1098/rstb.2010.0271.
Late onset is a common hallmark character of numerous disorders including human neurodegenerative maladies such as Huntington's, Parkinson's and Alzheimer's diseases. Why these diseases manifest in aged individuals and why distinct disorders share strikingly similar emergence patterns were until recently unsolved enigmas. During the past decade, invertebrate-based studies indicated that the insulin/IGF signalling pathway (IIS) mechanistically links neurodegenerative-associated toxic protein aggregation and ageing; yet, until recently it was unclear whether this link is conserved from invertebrates to mammals. Recent studies performed in Alzheimer's mouse models indicated that ageing alteration by IIS reduction slows the progression of Alzheimer's-like disease, protects the brain and mitigates the behavioural, pathological and biochemical impairments associated with the disease. Here, we review these novel studies and discuss the potential of ageing alteration as a therapeutic approach for the treatment of late onset neurodegeneration.
迟发性是许多疾病的共同特征标志，包括人类神经退行性疾病，如亨廷顿氏病、帕金森氏病和阿尔茨海默氏病。为什么这些疾病会在老年人中出现，为什么不同的疾病会有如此惊人相似的发病模式，直到最近仍是未解之谜。在过去的十年中，基于无脊椎动物的研究表明，胰岛素/IGF 信号通路（IIS）在机制上把与神经退行性相关的毒性蛋白聚集和衰老联系起来；然而，直到最近，人们还不清楚这种联系是否从无脊椎动物到哺乳动物都是保守的。最近在阿尔茨海默病小鼠模型中进行的研究表明，通过降低 IIS 来改变衰老速度可以减缓类似阿尔茨海默病的疾病进展，保护大脑并减轻与疾病相关的行为、病理和生化损伤。在这里，我们回顾了这些新的研究，并讨论了衰老改变作为治疗迟发性神经退行性变的一种治疗方法的潜力。
