Glabe Charles G, Kayed Rakez
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Neurology. 2006 Jan 24;66(2 Suppl 1):S74-8. doi: 10.1212/01.wnl.0000192103.24796.42.
Recent findings indicate that soluble amyloid oligomers may represent the primary pathologic species in degenerative diseases. These amyloid oligomers share common structural features and the ability to permeabilize membranes, suggesting that they also share a common primary mechanism of pathogenesis. Membrane permeabilization by amyloid oligomers may initiate a common group of downstream pathologic processes, including intracellular calcium dyshomeostasis, production of reactive oxygen species, altered signaling pathways, and mitochondrial dysfunction that represent key effectors of cellular dysfunction and cell death in amyloid-associated degenerative disease, such as sporadic inclusion-body myositis.
最近的研究结果表明,可溶性淀粉样寡聚体可能是退行性疾病中的主要病理物质。这些淀粉样寡聚体具有共同的结构特征和使膜通透的能力,这表明它们也具有共同的主要发病机制。淀粉样寡聚体导致的膜通透可能引发一组常见的下游病理过程,包括细胞内钙稳态失调、活性氧的产生、信号通路改变以及线粒体功能障碍,这些都是淀粉样蛋白相关退行性疾病(如散发性包涵体肌炎)中细胞功能障碍和细胞死亡的关键效应器。