| First Author | Fortun J | Year | 2006 |
| Journal | Neurobiol Dis | Volume | 22 |
| Issue | 1 | Pages | 153-64 |
| PubMed ID | 16326107 | Mgi Jnum | J:129218 |
| Mgi Id | MGI:3768890 | Doi | 10.1016/j.nbd.2005.10.010 |
| Citation | Fortun J, et al. (2006) Alterations in degradative pathways and protein aggregation in a neuropathy model based on PMP22 overexpression. Neurobiol Dis 22(1):153-64 |
| abstractText | 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. |
