| Autor: |
Yun J. Kim, Ellen Sapp, Benjamin G. Cuiffo, Lindsay Sobin, Jennifer Yoder, Kimberly B. Kegel, Zheng-Hong Qin, Peter Detloff, Neil Aronin, Marian DiFiglia |
| Jazyk: |
angličtina |
| Rok vydání: |
2006 |
| Předmět: |
|
| Zdroj: |
Neurobiology of Disease, Vol 22, Iss 2, Pp 346-356 (2006) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2005.11.012 |
| Popis: |
N-terminal mutant huntingtin (N-mhtt) fragments form inclusions and cause cell death in vitro. Mutant htt expression stimulates autophagy and increases levels of lysosomal proteases. Here, we show that lysosomal proteases, cathepsins D, B and L, affected mhtt processing and levels of cleavage products (cp) known as A and B, which form inclusions. Adding inhibitors of cathepsin D, B and L to clonal striatal cells reduced mhtt, especially mhtt fragment cp A. Mutant htt fully degraded in cathepsin-L-treated lysates but formed stable N-mhtt fragments upon exposure to cathepsin D. Mutagenesis analysis of htt cDNA suggested that cathepsin D and the protease for cp A may cleave htt in the same region. Brain lysates from HD knock-in mice expressed N-mhtt fragments that accumulated with cathepsin D treatment and declined with aspartyl protease inhibition. Findings implicate lysosomal proteases in formation of N-mhtt fragments and clearance of mhtt. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full Text from ScienceDirect