Alzheimer's disease: which type of amyloid-preventing drug agents to employ?

作者：Jang Hyunbum; Connelly Laura; Arce Fernando Teran; Ramachandran Srinivasan; Lal Ratnesh; Kagan Bruce L^*; Nussinov Ruth

来源：Physical Chemistry Chemical Physics, 2013, 15(23): 8868-8877.

DOI：10.1039/c3cp00017f

The current paradigm in the amyloid hypothesis brands small beta-amyloid (A beta) oligomers as the toxic species in Alzheimer's disease (AD). These oligomers are fibril-like; contain beta-sheet structure, and present exposed hydrophobic surface. Oligomers with this motif are capable of penetrating the cell membrane, gathering to form toxic ion channels. Current agents suppressing precursor A beta cleavage have only met partial success; and to date, those targeting the peptides and their assemblies in the aqueous environment of the extracellular space largely fail in clinical trials. One possible reason is failure to reach membrane-embedded targets of disease 'infected' cells. Here we provide an overview, point to the need to account for the lipid environment when aiming to prevent the formation of toxic channels, and propose a combination therapy to target the species spectrum.

• 出版日期2013