TOP ＞ 第3回日本神経化学会優秀賞受賞講演

第3回日本神経化学会優秀賞受賞講演 2E-日本神経化学会優秀賞 The development of agents for the preventives and therapeutics of Alzheimer's disease based on oligomer hypothesis Ono Kenjiro Department of Neurology, Showa University School of Medicine Alzheimer's disease（AD）is the most common neurodegenerative disorder in the aged people. Currently, no disease-modifying therapeutic agents are available for AD patients. Alzheimer's disease（AD）is characterized by the accumulation of amyloid plaques formed by the amyloid β-protein（Aβ）, a 40-42 amino acid peptide and neurofibrillary tangles, composed of paired helical filaments, the principal component of which is tau. Amyloid β-protein（Aβ）is the primary component of amyloid plaques, and has been suggested to be responsible for the pathogenesis of AD（amyloid hypothesis）. Aβ molecules tend to aggregates to form oligomers, protofibrils（PF）, and Aβ fibrils. Although these Aβ aggregates may cause neuronal injury, recent evidence supports the hypothesis that intermediate aggregates of Aβ, such as PF and oligomers play a seminal role in AD（oligomer hypothesis）. Thus, the inhibition of the oligomerization of Aβ has been suggested as a possible therapeutic target for the fundamental treatment of AD. We summarize here recent efforts to produce therapeutic drugs targeting Aβ oligomerization. Recently, we found that various compounds such as wine-related polyphenols and rifampicin inhibited the Aβ oligomerizaition and reduced neuronal and synaptic toxicities in vitro and in vivo. Although initial trials of some anti-aggregation agents have failed, they could be key molecules for the development of preventives and therapeutics for AD.