| First Author | Zhang Q | Year | 2009 |
| Journal | J Neurochem | Volume | 109 |
| Issue | 2 | Pages | 476-84 |
| PubMed ID | 19200347 | Mgi Jnum | J:149265 |
| Mgi Id | MGI:3848117 | Doi | 10.1111/j.1471-4159.2009.05959.x |
| Citation | Zhang Q, et al. (2009) Role of caspase-3 in tau truncation at D421 is restricted in transgenic mouse models for tauopathies. J Neurochem 109(2):476-84 |
| abstractText | Truncated tau is widely detected in Alzheimer's disease brain, and caspase-3 has been considered as a major executioner for tau truncation at aspartate421 (D421), according to its capability of cleaving recombinant tau in vitro. Here we investigated the relationship between D421 truncated tau and caspase-3 in two transgenic mouse models for tauopathies. In adult transgenic mice, activated caspase-3 could not be detected in neurons containing truncated tau, with the exception of a few glia-like cells or neurons in postnatal mice. Caspase-3 expression exhibited a dramatic decrease at the early development stage, and kept at constantly low levels during adult stages in both wild type and transgenic mice. On the other hand, co-incubating brain homogenates from adult tau transgenic mice and ethanol-treated postnatal mice promoted tau truncation at D421, which was mildly reduced by caspase inhibitor, but completely suppressed by phosphatase inhibitor, indicating that hyperphosphorylated tau becomes a poor substrate for truncation at D421. Taken together, our study shows that insufficient caspase-3 expression and hyperphosphorylated status of tau in the adult transgenic mouse brain restrict caspase-3 as an efficient enzyme for tau truncation in vivo. Clearly, there is a caspase-3 independent mechanism responsible for tau truncation at D421 in these models. |
