Departments of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA.
Curr Neuropharmacol. 2011 Dec;9(4):674-84. doi: 10.2174/157015911798376181.
Amyloidopathies cause neurodegeneration in a substantial portion of the elderly population. Improvements in long term health care have made elderly individuals a large and growing demographic group, marking these diseases as a major public health concern. Alzheimer's Disease (AD) is the most studied form of neurodegenerative amyloidopathy. Although our understanding of AD is far from complete, several decades of research have advanced our knowledge to the point where it is conceivable that some form of disease modifying therapy may be available in the near future. These advances have been built on a strong mechanistic understanding of the disease from its underlying genetics, molecular biology and clinical pathology. Insights derived from the study of other neurodegenerative diseases, such as some forms of frontotemporal dementia, have been critical to this process. This knowledge has allowed researchers to construct animal models of the disease process that have paved the way towards the development of therapeutics. However, what was once thought to be a straightforward problem has evolved into a series of disappointing outcomes. Examination of pathways common to all neurodegenerative diseases, including the cellular mechanisms that clear misfolded proteins and their regulation, may be the best way to move forward.
淀粉样变疾病会导致相当一部分老年人的神经退行性变。长期医疗保健的改善使老年人群成为一个庞大且不断增长的人口群体，这使得这些疾病成为一个主要的公共卫生关注点。阿尔茨海默病（AD）是研究最多的神经退行性淀粉样变形式。尽管我们对 AD 的理解还远远不够，但几十年的研究已经使我们的知识发展到了可以想象的地步，即在不久的将来可能会有某种形式的疾病修饰疗法。这些进展建立在对疾病从潜在遗传学、分子生物学和临床病理学基础上的强大机制理解之上。从其他神经退行性疾病（如某些形式的额颞叶痴呆）的研究中获得的见解对这一过程至关重要。这些知识使研究人员能够构建疾病过程的动物模型，为治疗方法的发展铺平了道路。然而，曾经被认为是一个简单的问题已经演变成一系列令人失望的结果。检查所有神经退行性疾病共有的途径，包括清除错误折叠蛋白的细胞机制及其调节，可能是前进的最佳途径。
