期刊
EXPERIMENTAL NEUROLOGY
卷 184, 期 1, 页码 131-140出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S0014-4886(03)00393-5
关键词
tau; four-repeat; isoform; aggregation; microtubule assembly; axonal; glial tau; neurodegeneration; dementia; pick body
资金
- NIA NIH HHS [P01 AG17216] Funding Source: Medline
- NATIONAL INSTITUTE ON AGING [P01AG017216] Funding Source: NIH RePORTER
A novel mutation in exon 9 of tau, I260V, is associated with a clinical syndrome consistent with frontotemporal dementia with extensive tau pathology; however, neurofibrillary tangles and Pick bodies are absent. Significantly, Sarkosyl- insoluble tau extracted from affected brain tissue consisted almost exclusively of four-repeat isoforms. Consistent with these findings, in vitro biochemical assays demonstrated that the I260V mutation causes a selective increase in tau aggregation and a decrease in tau-induced microtubule assembly with four-repeat isoforms only. The contrasting pathology and biochemical effects of this mutation suggest a different disease mechanism from the other exon 9 mutations and demonstrates the critical role for the first microtubule-binding domain in tau-promoted microtubule assembly and the pathogenic aggregation of tau. (C) 2003 Elsevier Inc. All rights reserved.
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