Hamazaki H
Department of Biology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
FEBS Lett. 1996 Nov 18;397(2-3):313-5. doi: 10.1016/s0014-5793(96)01202-1.
The cerebral deposition of 40-42 residue amyloid beta-protein (Abeta) is a characteristic of Alzheimer's disease. Cathepsin D is possibly involved in the intracellular clearance of Abeta (Hamazaki, H. (1996) FEBS Lett., in press). The present work shows that cathepsin D hydrolyzes wild-type Abeta 20 times faster than a variant Abeta with a substitution at residue 21 from Ala to Gly. Since the substitution has been linked to familial Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis (Hendriks et al. (1992) Nature Genet. 1, 218-221), the present observations suggest that the inefficient elimination of Abeta by cathepsin D is capable of being one of causes of the amyloid fibril formation.
40 - 42个氨基酸残基的β淀粉样蛋白（Aβ）在大脑中的沉积是阿尔茨海默病的一个特征。组织蛋白酶D可能参与了Aβ的细胞内清除过程（滨崎博（1996年），《欧洲生物化学学会联合会快报》，即将发表）。目前的研究表明，组织蛋白酶D水解野生型Aβ的速度比在第21位残基由丙氨酸替换为甘氨酸的变异型Aβ快20倍。由于这种替换与家族性阿尔茨海默病和淀粉样变性遗传性脑出血有关（亨德里克斯等人（1992年），《自然遗传学》1，218 - 221），目前的观察结果表明，组织蛋白酶D对Aβ清除效率低下可能是淀粉样纤维形成的原因之一。
