Amyloid binding ligands as Alzheimer's disease therapies.

摘要: Abstract Extracellular senile plaques (SPs) are hallmark brain lesions of sporadic Alzheimer’s disease (AD) and the likely consequence genetic mutations that cause familial AD by increasing production amyloidogenic amyloid-β (Aβ). Although Aβ vaccines inhibitors secretases potential therapies, multifaceted strategies may be needed to effectively interrupt amyloidosis prevent/arrest AD. One such strategy is inhibition fibrillization as a therapy for Certain amyloid-binding molecules, Congo red (CR) chrysamine G (CG) Thioflavin S (TS) have been shown bind SPs with high affinity they can also arrest formation fibrils; however, CR, CG TS unsuitable because do not cross blood barrier (BBB). Therefore, we generated novel derivatives specifically recognize fibrillar in vitro, fibrils, BBB transgenic (TG) mice model amyloidosis. As proof their ability specificity fibrils vivo, show following intravenous injection TG these compounds label AD-like deposits Aβ. Furthermore, demonstrate derivative IMSB binds comprised Aβ40 much higher than Aβ42 whereas TDZM shows opposite affinity. Moreover, but selectively neurofibrillary tangles. Significantly both inhibit test tubes cultured cells. Thus, small amyloid binding molecules which therapeutic agents treatment