Aggresome Formation in Neuropathy Models Based on Peripheral Myelin Protein 22 Mutations
Alterations in peripheral myelin protein 22 (PMP22) gene expression are associated with demyelinating peripheral neuropathies. Overexpression of wild type (wt) PMP22 or inhibition of proteasomal degradation lead to the formation of aggresomes, intracellular ubiquitinated PMP22 aggregates. Aggresome...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2002-07-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996102905000 |
| _version_ | 1818648754415206400 |
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| author | Mary C. Ryan Eric M. Shooter Lucia Notterpek |
| author_facet | Mary C. Ryan Eric M. Shooter Lucia Notterpek |
| author_sort | Mary C. Ryan |
| collection | DOAJ |
| description | Alterations in peripheral myelin protein 22 (PMP22) gene expression are associated with demyelinating peripheral neuropathies. Overexpression of wild type (wt) PMP22 or inhibition of proteasomal degradation lead to the formation of aggresomes, intracellular ubiquitinated PMP22 aggregates. Aggresome formation has now been observed with two mutant PMP22s, the Tr- and TrJ-PMP22 when the proteasome is inhibited. The formation of these aggresomes required intact microtubules and involved the recruitment of chaperones, including Hsp40, Hsp70, and αB-crystallin. Spontaneously formed ubiquitinated PMP22 aggregates were also observed in Schwann cells of homozygous TrJ mice. Significant upregulation of both the ubiquitin-proteasomal and lysosomal pathways occurred in affected nerves suggesting that two pathways of PMP22 degradation are present. Thus, the presence of aggresomes appears to be a common finding in neuropathy models of PMP22 overexpression and of some point mutations known to cause neuropathy in mice and humans. |
| first_indexed | 2024-12-17T01:23:27Z |
| format | Article |
| id | doaj.art-ee47366d9cd9464a8967c0de60d60003 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T01:23:27Z |
| publishDate | 2002-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-ee47366d9cd9464a8967c0de60d600032022-12-21T22:08:46ZengElsevierNeurobiology of Disease1095-953X2002-07-01102109118Aggresome Formation in Neuropathy Models Based on Peripheral Myelin Protein 22 MutationsMary C. Ryan0Eric M. Shooter1Lucia Notterpek2Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305-5125; Department of Neuroscience, College of Medicine, University of Florida, McKnight Brain Institute, Gainesville, Florida, 32610Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305-5125; Department of Neuroscience, College of Medicine, University of Florida, McKnight Brain Institute, Gainesville, Florida, 32610Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305-5125; Department of Neuroscience, College of Medicine, University of Florida, McKnight Brain Institute, Gainesville, Florida, 32610Alterations in peripheral myelin protein 22 (PMP22) gene expression are associated with demyelinating peripheral neuropathies. Overexpression of wild type (wt) PMP22 or inhibition of proteasomal degradation lead to the formation of aggresomes, intracellular ubiquitinated PMP22 aggregates. Aggresome formation has now been observed with two mutant PMP22s, the Tr- and TrJ-PMP22 when the proteasome is inhibited. The formation of these aggresomes required intact microtubules and involved the recruitment of chaperones, including Hsp40, Hsp70, and αB-crystallin. Spontaneously formed ubiquitinated PMP22 aggregates were also observed in Schwann cells of homozygous TrJ mice. Significant upregulation of both the ubiquitin-proteasomal and lysosomal pathways occurred in affected nerves suggesting that two pathways of PMP22 degradation are present. Thus, the presence of aggresomes appears to be a common finding in neuropathy models of PMP22 overexpression and of some point mutations known to cause neuropathy in mice and humans.http://www.sciencedirect.com/science/article/pii/S0969996102905000aggresomesPMP22ubiquitin-proteasome pathwayTrembler miceprotein degradationSchwann cells |
| spellingShingle | Mary C. Ryan Eric M. Shooter Lucia Notterpek Aggresome Formation in Neuropathy Models Based on Peripheral Myelin Protein 22 Mutations Neurobiology of Disease aggresomes PMP22 ubiquitin-proteasome pathway Trembler mice protein degradation Schwann cells |
| title | Aggresome Formation in Neuropathy Models Based on Peripheral Myelin Protein 22 Mutations |
| title_full | Aggresome Formation in Neuropathy Models Based on Peripheral Myelin Protein 22 Mutations |
| title_fullStr | Aggresome Formation in Neuropathy Models Based on Peripheral Myelin Protein 22 Mutations |
| title_full_unstemmed | Aggresome Formation in Neuropathy Models Based on Peripheral Myelin Protein 22 Mutations |
| title_short | Aggresome Formation in Neuropathy Models Based on Peripheral Myelin Protein 22 Mutations |
| title_sort | aggresome formation in neuropathy models based on peripheral myelin protein 22 mutations |
| topic | aggresomes PMP22 ubiquitin-proteasome pathway Trembler mice protein degradation Schwann cells |
| url | http://www.sciencedirect.com/science/article/pii/S0969996102905000 |
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