Yen S, Easson C, Nacharaju P, Hutton M, Yen S H
Department of Pharmacology, Birdsall Medical Research Building, Mayo Clinic Jacksonville, FL 32224, USA.
FEBS Lett. 1999 Nov 12;461(1-2):91-5. doi: 10.1016/s0014-5793(99)01427-1.
Frontal temporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) is caused by splice site and missense mutations in the tau gene, and characterized by the accumulation of filamentous tau in cerebral neurons and glia. The missense mutations reduce the ability of tau to promote microtubule assembly and increase the ability of tau to form filaments. In this report we demonstrate that mutants V337M and R406W are less susceptible than mutant P301L or corresponding wild type tau to degradation by calpain I. The differences were at least in part due to changes in accessibility of a cleavage site located about 100 amino acids off the carboxy-terminus. The results suggest that the pathogenesis of some forms of FTDP-17 may involve tau accumulation due to decreased proteolytic degradation.
与17号染色体相关的额颞叶痴呆和帕金森综合征（FTDP - 17）由tau基因的剪接位点和错义突变引起，其特征是丝状tau在脑神经元和神经胶质细胞中积累。错义突变降低了tau促进微管组装的能力，并增加了tau形成细丝的能力。在本报告中，我们证明突变体V337M和R406W比突变体P301L或相应的野生型tau更不易被钙蛋白酶I降解。这些差异至少部分是由于位于羧基末端约100个氨基酸处的切割位点可及性的变化。结果表明，某些形式的FTDP - 17的发病机制可能涉及由于蛋白水解降解减少导致的tau积累。
