Title
Mutant HSPB8 causes protein aggregates and a reduced mitochondrial membrane potential in dermal fibroblasts from distal hereditary motor neuropathy patients Mutant HSPB8 causes protein aggregates and a reduced mitochondrial membrane potential in dermal fibroblasts from distal hereditary motor neuropathy patients
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Subject
Biology
Human medicine
Source (journal)
Neuromuscular disorders
Volume/pages
22(2012) :8 , p. 699-711
ISSN
0960-8966
ISI
000307619900004
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Missense mutations in the small heat shock protein HSPB8 cause distal hereditary motor neuropathy (dHMN) and axonal Charcot-Marie-Tooth disease (CMT2L). We previously demonstrated that, despite the ubiquitous expression of HSPB8, motor neurons appear to be predominantly affected by HSPB8 mutations. Here, we studied the effect of mutant HSPB8 in primary fibroblast cultures derived from dHMN patients skin biopsy. In early passage cultures, we observed in all patients fibroblasts HSPB8 protein aggregates that were not detected in control cells. After applying heat shock stress on the patients early passage cultured cells, the protein aggregates coalesced into larger formations, while in control cells a homogenous upregulation of HSPB8 protein expression was seen. We also found a reduction in the mitochondrial membrane potential in the early passage cultures. After three months in culture, the number of cells with aggregates had become indistinguishable from that in controls and the mitochondrial membrane potential had returned to normal. These results emphasize the possible drawbacks of using patients non-neuronal cells to study neuropathological disease mechanisms.
E-info
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