Currais Antonio, Fischer Wolfgang, Maher Pamela, Schubert David
Salk Institute for Biological Studies, La Jolla, California, USA
Salk Institute for Biological Studies, La Jolla, California, USA.
FASEB J. 2017 Jan;31(1):5-10. doi: 10.1096/fj.201601184.
Age is, by far, the greatest risk factor for Alzheimer's disease (AD), yet few AD drug candidates have been generated that target pathways specifically associated with the aging process itself. Two ubiquitous features of the aging brain are the intracellular accumulation of aggregated proteins and inflammation. As intraneuronal amyloid protein is detected before markers of inflammation, we argue that old, age-associated, aggregated proteins in neurons can induce inflammation, resulting in multiple forms of brain toxicities. The consequence is the increased risk of old, age-associated, neurodegenerative diseases. As most of these diseases are associated with the accumulation of aggregated proteins, it is possible that any therapeutic that reduces intracellular protein aggregation will benefit all.-Currais, A., Fischer, W., Maher, P., Schubert, D. Intraneuronal protein aggregation as a trigger for inflammation and neurodegeneration in the aging brain.
到目前为止，年龄是阿尔茨海默病（AD）最大的风险因素，但针对与衰老过程本身特别相关的途径而研发的AD候选药物却很少。衰老大脑的两个普遍特征是聚集蛋白的细胞内积累和炎症。由于在炎症标志物出现之前就能检测到神经元内的淀粉样蛋白，我们认为神经元中与年龄相关的老化聚集蛋白会诱发炎症，从而导致多种形式的脑毒性。其结果是患与年龄相关的老年神经退行性疾病的风险增加。由于这些疾病大多与聚集蛋白的积累有关，所以任何能减少细胞内蛋白聚集的治疗方法都可能有益。——库赖斯，A.，菲舍尔，W.，马赫，P.，舒伯特，D. 神经元内蛋白聚集作为衰老大脑炎症和神经退行性变的触发因素
