Premium
Proteomic analysis in giant axonal neuropathy: New insights into disease mechanisms
Author(s) -
Mussche Silke,
De Paepe Boel,
Smet Joél,
Devreese Katrien,
Lissens Willy,
Rasic Vedrana Milic,
Murnane Matthew,
Devreese Bart,
Van Coster Rudy
Publication year - 2012
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.23306
Subject(s) - cytoskeleton , intermediate filament , biology , ribosomal protein , microbiology and biotechnology , formins , actin , proteomics , gene , actin cytoskeleton , cell , genetics , ribosome , rna
: Giant axonal neuropathy (GAN) is a progressive hereditary disease that affects the peripheral and central nervous systems. It is characterized morphologically by aggregates of intermediate filaments in different tissues. Mutations have been reported in the gene that codes for gigaxonin. Nevertheless, the underlying molecular mechanism remains obscure. Methods : Cell lines from 4 GAN patients and 4 controls were analyzed by iTRAQ. Results : Among the dysregulated proteins were ribosomal protein L29, ribosomal protein L37, galectin‐1, glia‐derived nexin, and aminopeptidase N. Also, nuclear proteins linked to formin‐binding proteins were found to be dysregulated. Although the major role of gigaxonin is reported to be degradation of cytoskeleton‐associated proteins, the amount of 76 structural cytoskeletal proteins was unaltered. Conclusions : Several of the dysregulated proteins play a role in cytoskeletal reorganization. Based on these findings, we speculate that disturbed cytoskeletal regulation is responsible for formation of aggregates of intermediate filaments. Muscle Nerve 46: 246–256, 2012