Niikura Takako, Hashimoto Yuichi, Tajima Hirohisa, Ito Yuko, Nishimoto Ikuo
Department of Pharmacology, KEIO University School of Medicine.
Nihon Ronen Igakkai Zasshi. 2003 Jan;40(1):36-40. doi: 10.3143/geriatrics.40.36.
Neuronal cell death accounts for the clinical manifestations in Alzheimer's disease (AD). To establish the curative therapy of AD, neuroprotection is one of the primary therapeutic targets, and the elucidation of the mechanism of neuronal cell death is mandatory. Detailed characterization of neuronal cell death caused by familial AD (FAD)-linked mutant genes revealed that different cell death pathways are evoked by different types of mutants. Humanin (HN), a newly identified neuroprotective peptide, suppresses neuronal cell death caused by all known FAD mutants and A beta, while it has no effect on neuronal cell death caused by AD-irrelevant insults. The functional target of HN is the antagonism to neuronal death, not the modulation of A beta production, suggesting that HN-based medication can be combined with other remedies targeting A beta. HN is a promising seed for a novel therapy aiming at complete cure of AD through the suppression of neuronal loss.
神经元细胞死亡是阿尔茨海默病（AD）临床表现的原因。为了建立AD的治疗方法，神经保护是主要治疗靶点之一，阐明神经元细胞死亡机制是必不可少的。对由家族性AD（FAD）相关突变基因引起的神经元细胞死亡的详细表征表明，不同类型的突变体引发不同的细胞死亡途径。人胰岛素（HN）是一种新发现的神经保护肽，可抑制所有已知FAD突变体和Aβ引起的神经元细胞死亡，而对与AD无关的损伤引起的神经元细胞死亡没有影响。HN的功能靶点是对抗神经元死亡，而不是调节Aβ的产生，这表明基于HN的药物可以与其他针对Aβ的治疗方法联合使用。HN是一种有前途的种子，有望通过抑制神经元丢失实现AD的完全治愈。
