Fraser P E, Yang D S, Yu G, Lévesque L, Nishimura M, Arawaka S, Serpell L C, Rogaeva E, St George-Hyslop P
Centre for Research in Neurodegenerative Diseases, University of Toronto, Ont, Canada.
Biochim Biophys Acta. 2000 Jul 26;1502(1):1-15. doi: 10.1016/s0925-4439(00)00028-4.
Numerous missense mutations in the presenilins are associated with the autosomal dominant form of familial Alzheimer disease. Presenilin genes encode polytopic transmembrane proteins, which are processed by proteolytic cleavage and form high-molecular-weight complexes under physiological conditions. The presenilins have been suggested to be functionally involved in developmental morphogenesis, unfolded protein responses and processing of selected proteins including the beta-amyloid precursor protein. Although the underlying mechanism by which presenilin mutations lead to development of Alzheimer disease remains elusive, one consistent mutational effect is an overproduction of long-tailed amyloid beta-peptides. Furthermore, presenilins interact with beta-catenin to form presenilin complexes, and the physiological and mutational effects are also observed in the catenin signal transduction pathway.
早老素中的众多错义突变与常染色体显性遗传形式的家族性阿尔茨海默病相关。早老素基因编码多跨膜蛋白，这些蛋白经蛋白水解切割处理，并在生理条件下形成高分子量复合物。早老素被认为在发育形态发生、未折叠蛋白反应以及包括β-淀粉样前体蛋白在内的特定蛋白的加工过程中发挥功能作用。尽管早老素突变导致阿尔茨海默病发生的潜在机制仍不清楚，但一个一致的突变效应是长尾淀粉样β肽的过度产生。此外，早老素与β-连环蛋白相互作用形成早老素复合物，并且在连环蛋白信号转导途径中也观察到了生理和突变效应。
