| Autor: |
Jenny Fortun, Jocelyn C. Go, Jie Li, Stephanie A. Amici, William A. Dunn, Jr., Lucia Notterpek |
| Jazyk: |
angličtina |
| Rok vydání: |
2006 |
| Předmět: |
|
| Zdroj: |
Neurobiology of Disease, Vol 22, Iss 1, Pp 153-164 (2006) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2005.10.010 |
| Popis: |
Charcot–Marie–Tooth disease type 1A (CMT1A) is commonly associated with duplication of the peripheral myelin protein 22 (PMP22) gene. Mice expressing seven copies of the human PMP22, termed C22, suffer from a demyelinating neuropathy and display phenotypic traits of CMT1A. In this article, we investigate whether protein aggregates play a role in the CMT1A-like pathology of C22 mice. Utilizing biochemical and immunochemical tools, we found slowed turnover rate of the newly-synthesized PMP22 and the presence of cytoplasmic protein aggregates in affected nerves. The formation of these aggregates correlates with reduced proteasome activity and the accumulation of detergent-insoluble ubiquitinated substrates. A fraction of the aggregates associates with autophagosomes and lysosomes. Together, these data indicate that as a result of missorting and inefficient proteasomal degradation, the aggregation of PMP22 and recruitment of autophagosomes and lysosomes are key factors in the subcellular pathogenesis of CMT1A neuropathies. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full Text from ScienceDirect