CHIP-Less Mice Accumulate Tau

The accumulation of the microtubule-associated protein tau is associated with several neurodegenerative diseases, and in the case of FTDP-17 (frontotemporal dementia with parkinsonism-linked to chromosome 17), tau mutations are sufficient to produce neurodegeneration. This week, Dickey et al. focused on the role of the cochaperone and ubiquitin ligase CHIP (C terminus of the Hsc70-interacting protein) in degradation of phosphorylated tau. In CHIP-/- mice, about half of the knock-out mice showed motor deficits and small size. These symptomatic knock-out mice had elevated tau levels and thus were used for the experiments. In these mice, there was an accumulation of non-aggregated, ubiquitin-negative, hyperphosphorylated tau. Overexpression of mutant human tau (P301L) caused accumulation of phospho-tau but was not sufficient to produce aggregates or "pre-tangle" structures. Thus, the authors suggest that polyubiquitination of tau by CHIP contributes to insoluble tau aggregates and is part of an adaptive neuronal response.

###

Tips from The Journal of Neuroscience
Chad A. Dickey, Mei Yue, Wen-Lang Lin, Dennis W. Dickson, Judith H. Dunmore, Wing C. Lee, Cynthia Zehr, Gemma West, Songsong Cao, Amber M. K. Clark, Guy A. Caldwell, Kim A. Caldwell, Christopher Eckman, Cam Patterson, Michael Hutton, and Leonard Petrucelli

Contact: Sara Harris
Society for Neuroscience
(责任编辑：泉水)

搜索

热门标签:

CHIP-Less Mice Accumulate Tau